Antiviral drugs

Abstract

The present invention addresses the problem of providing an antiviral agent that comprises probiotics as an active ingredient and exerts an effective antiviral effect even on complex infection with a virus and a pathogenic bacterium.　As an antiviral agent, use is made of an agent that comprises one or more bacterial strains belonging to the genus Lactobacillus, said strains having a 16S rRNA gene that has 90% or higher identity to the nucleotide sequence represented by SEQ ID NO: 1 and also having an expression enhancing action on an antiviral factor and / or an expression reducing action on a downregulator of an antiviral factor.

Description

[Technical Field] 【0001】 The present invention relates to an antiviral agent containing an antiviral probiotic (preferably an immunobiotic [i.e., a probiotic having mucosal immunomodulatory function such as that of the intestinal mucosa]) as an active ingredient. [Background technology] 【0002】 Probiotics are live microorganisms that act on the normal bacterial flora within the host mammal (especially in the intestinal tract), improving its balance and thereby benefiting the mammalian body. Probiotics are known to exert bactericidal and immune-boosting effects against viral and pathogenic bacterial infections by inducing the production of bactericidal substances, competitive intake of nutrients, competition for attachment sites, and promotion or inhibition of metabolic enzyme activity. 【0003】 Specific examples of probiotics include lactic acid bacteria such as those belonging to the genera Lactobacillus, Biffidobacterium, Enterococcus, Leuconostoc, and Pediococcus. Specifically, cytoplasmic fractions of lactic acid bacteria and immunostimulatory compositions containing cytoplasmic fractions have been reported (Patent Document 1). Furthermore, freeze-dried powder of Lactobacillus brevis subsp. coagulans has been reported to enhance the expression of interferon (IFN)-α and IFN-γ, and to activate natural killer (NK) cells (Patent Document 2). In addition, spore-forming lactic acid bacteria such as Bacillus coagulans have been reported to have antiviral effects against infections caused by common cold viruses and influenza viruses (Patent Document 3). Furthermore, it has been reported that lactic acid bacteria such as Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus fermentum, Lactobacillus paracasei, and Lactobacillus gasseri can be used to prevent and treat viral infections (Patent Document 4). In addition, it has been reported that using Lactobacillus brevis in combination with Enterococcus faecalis exhibits excellent preventive effects against influenza virus infections (Patent Document 5). However, until now, no probiotics that effectively exert antiviral effects in combined infections of viruses and pathogenic bacteria have been known. [Prior art documents] [Patent Documents] 【0004】 [Patent Document 1] Japanese Patent Application Publication No. 5-252900 [Patent Document 2] Japanese Patent Application Publication No. 6-206826 [Patent Document 3] Japanese Patent Publication No. 2008-13543 [Patent Document 4] Special Publication No. 2009-511470 [Patent Document 5] Japanese Patent Publication No. 2012-136450 [Overview of the Initiative] [Problems that the invention aims to solve] 【0005】 The object of the present invention is to provide an antiviral agent containing a probiotic as an active ingredient that effectively exhibits antiviral effects even in cases of combined infections of viruses and pathogenic bacteria. [Means for solving the problem] 【0006】 The inventors of this invention have been diligently conducting research to solve the above problems. In the process, they first identified two factors (IFN-β and Mx1) as indicators for evaluating the antiviral activity of probiotics. Next, from among 116 Lactobacillus salivarius (also called "Ligilactobacillus salivarius") strains isolated from the intestinal tract of pigs, they selected Lactobacillus bacterial strains that exhibited antiviral activity using the expression levels of the two factors mentioned above as indicators. Furthermore, they found that the selected antiviral Lactobacillus bacterial strains have the effect of enhancing the expression of antiviral factors and reducing the expression of factors that downregulate antiviral factors, and that they effectively exert antiviral effects even in co-infections of viruses and pathogenic bacteria. Furthermore, it was confirmed that a specific Lactobacillus bacterial strain exhibiting wakame assimilation ability possesses a 16S rRNA gene with the same nucleotide sequence as the selected antiviral Lactobacillus bacterial strain, and that it enhances the expression of antiviral factors. In addition, a Lactobacillus plantarum strain (also called "Lactiplantibacillus plantarum"), which is a different species from Lactobacillus salivarius and possesses a 16S rRNA gene with at least 90% identity to the nucleotide sequence of the 16S rRNA gene of Lactobacillus salivarius that exhibited antiviral effects (i.e., the nucleotide sequence of Sequence ID No. 1), was identified. and Lactobacillus mucosae strain We also confirmed that it possesses antiviral effects. This invention was completed based on these findings. 【0007】 In other words, the present invention is as follows: [1] An antiviral agent characterized by containing one or more strains of Lactobacillus bacteria that have a 16S rRNA gene having at least 90% identity with the nucleotide sequence shown in Sequence ID No. 1, and that have an effect of enhancing the expression of antiviral factors and / or reducing the expression of downregulatory factors of antiviral factors. 〔2〕The antiviral factor is one or more antiviral factors selected from interferon (IFN)-β, IFN-λ, Mx1 (MX dynamin like GTPase 1), OAS1 (2'-5'-oligoadenylate synthetase 1), RNaseL, PKR (Protein kinase R), and RIG-I (Retinoic acid inducible gene-I), and the downregulatory factor of the antiviral factor is one or two downregulatory factors of the antiviral factor selected from A20 and Tollip (Toll-interacting protein). The antiviral agent according to 〔1〕 above. 〔3〕The Lactobacillus strain has an action of enhancing the expression of one or more receptors selected from TLR (Toll-like receptor) 2, TLR4, and NOD2 (Nucleotide binding oligomerization domain-like receptor 2). The antiviral agent according to 〔1〕 or 〔2〕 above. 〔4〕The virus is a double-stranded RNA virus. The antiviral agent according to any one of 〔1〕 to 〔3〕 above. 〔5〕The Lactobacillus strain is the Entrustment Lactobacillus salivarius strain deposited as Accession No. NITE B P-03218; the Lactobacillus salivarius strain deposited as Accession No. NITE Entrustment P-03219; the Lactobacillus salivarius strain deposited as Accession No. NITE B P-03221; the Lactobacillus salivarius strain deposited as Accession No. NITE Entrustment Lactobacillus plantarum strain deposited as Accession No. NITE B P-03474; the Lactobacillus plantarum strain deposited as Accession No. NITE Entrustment Lactobacillus plantarum strain deposited as Accession No. NITE B P-03467; the Lactobacillus plantarum strain deposited as Accession No. NITE Entrustment Lactobacillus plantarum strain deposited as Accession No. NITE B P-03468; the Lactobacillus plantarum strain deposited as Accession No. NITE Entrustment Lactobacillus plantarum strain deposited as Accession No. NITE B P-03468; the Lactobacillus plantarum strain deposited as Accession No. NITE Entrustment Lactobacillus plantarum strain deposited as Accession No. NITEB Lactobacillus plantarum strain deposited as P-03466; recipient Entrustment number NITE B Lactobacillus plantarum strain deposited as P-03471; recipient Entrustment number NITE B Lactobacillus plantarum strain deposited as P-03469; recipient Entrustment number NITE B Lactobacillus plantarum strain deposited as P-03470; recipient Entrustment number NITE B Lactobacillus plantarum strain deposited as P-03472; and, recipient Entrustment number NITE B Lactobacillus plantarum strain deposited as P-03473 Mucosae strain; being one or more selected from the above, characterized in that it is any one of the antiviral agents described in any of the above [1] to [4]. [6] The antiviral agent according to any one of the above [1] to [5], characterized in that the Lactobacillus genus bacterial strain exhibits wakame assimilating ability. [7] The antiviral agent according to any one of the above [1] to [6], characterized in that it is a livestock feed or a food or drink. [8] Recipient Entrustment number NITE B Lactobacillus salivarius strain deposited as P-03218; recipient Entrustment number NITE B Lactobacillus salivarius strain deposited as P-03219; recipient Entrustment number NITE B Lactobacillus salivarius strain deposited as P-03221; recipient Entrustment number NITE B Lactobacillus plantarum strain deposited as P-03474; recipient Entrustment number NITE B Lactobacillus plantarum strain deposited as P-03467; recipient Entrustment number NITE B Lactobacillus plantarum strain deposited as P-03468; recipient Entrustment number NITEB Lactobacillus plantarum strain deposited as P-03466; Entrustment Number NITE B Lactobacillus plantarum strain deposited as P-03471; Entrustment Number NITE B Lactobacillus plantarum strain deposited as P-03469; Entrustment Number NITE B Lactobacillus plantarum strain deposited as P-03470; Entrustment Number NITE B Lactobacillus plantarum strain deposited as P-03472; or, Entrustment Number NITE B Lactobacillus deposited as P-03473. Mucosae KK. 【0008】 Another embodiment of the present invention is, A method for preventing and / or treating a viral infection, comprising the step of administering one or more Lactobacillus bacterial strains (hereinafter sometimes referred to as "the Lactobacillus bacterial strains") having a 16S rRNA gene (16S rDNA) that is at least 90% identical to the nucleotide sequence shown in Sequence ID No. 1, and having an effect of enhancing the expression of antiviral factors and / or reducing the expression of downregulatory factors of antiviral factors, to a subject (patient) who requires prevention and / or treatment of a viral infection (preferably a viral infection in a co-infection of a virus and pathogenic bacteria); or, One or more strains of the Lactobacillus genus in question, for use as antiviral agents; One or more strains of the Lactobacillus genus for use in antiviral applications; or one or more strains of the Lactobacillus genus for use in the prevention and / or treatment of viral infections; The use of one or more strains of the Lactobacillus genus in question for the manufacture of antiviral agents; or, Use of one or more strains of the Lactobacillus genus for the manufacture of agents for the prevention and / or treatment of viral infections; One could list these: [Effects of the Invention] 【0009】 The Lactobacillus strain in question has the effect of enhancing the expression of antiviral factors and reducing the expression of factors that downregulate antiviral factors, and effectively exerts antiviral effects even in co-infections of viruses and pathogenic bacteria. Furthermore, since the Lactobacillus strain in question is a symbiotic bacterial strain (i.e., a probiotic) that lives within the body of the host mammal (especially in the intestinal tract), unlike vaccines and antibiotics, it can effectively prevent and improve (treat) viral infections (preferably viral infections in co-infections of viruses and pathogenic bacteria) in humans and non-human mammals (especially livestock) with virtually no side effects. Moreover, if the Lactobacillus strain in question has the ability to assimilate seaweed, immunosinbiotics consisting of the seaweed-assimilated Lactobacillus strain in question (preferably an antiviral immunobiotic) and seaweed (a prebiotic) promote the growth of the bacterial strain, thereby allowing the antiviral effect of the Lactobacillus strain in question to be exerted more effectively. [Brief explanation of the drawing] 【0010】 [Figure 1] This figure shows the results of analyzing the expression levels of two antiviral factors (IFN-β [Figure 1A] and Mx1 [Figure 1B]) in porcine intestinal epithelial cell lines (PIE [Porcine Intestinal Epitheliocyte] cell lines) stimulated with Poly I:C. The time elapsed since stimulation with Poly I:C is shown. "*", "**", and "***" in the figure indicate statistically significant differences (p<0.05, p<0.01, and p<0.001) compared to the result at 0 hours. [Figure 2]This figure shows the results of analyzing the expression levels of two antiviral factors (IFN-β [vertical axis] and Mx1 [horizontal axis]) in PIE cell lines stimulated with 116 different Lactobacillus salivarius strains before stimulation with Poly I:C. Each plot (●) in the figure represents a different Lactobacillus salivarius strain. The arrows in the figure indicate strain #35, and the arrowheads indicate strain #58. [Figure 3] This figure shows the results of analyzing the expression levels of five receptors (TLR2 [Figure 3A], TLR3 [Figure 3B], TLR4 [Figure 3C], NOD1 [Figure 3D], and NOD2 [Figure 3E]) in PIE cell lines stimulated with strain #35 ("#35" in the figure) or strain #58 ("#58" in the figure). "*", "**", and "***" in the figure indicate statistically significant differences (p<0.05, p<0.01, and p<0.001) compared to the 0-hour result, respectively. [Figure 4] This figure shows the results of analyzing the expression levels of four antiviral factors (IFN-β [Figure 4A], IFN-λ [Figure 4B], Mx1 [Figure 4C], and OAS1 [Figure 4D]) in PIE cell lines stimulated with strain #35 ("#35" in the figure) or strain #58 ("#58" in the figure). "*", "**", and "***" in the figure indicate statistically significant differences (p<0.05, p<0.01, and p<0.001) compared to the 0-hour result, respectively. [Figure 5] This figure shows the results of analyzing the expression levels of three antiviral factors (RNaseL [Figure 5A], PKR [Figure 5B], and RIG-I [Figure 5C]) in PIE cell lines stimulated with strain #35 ("#35" in the figure) or strain #58 ("#58" in the figure). "**" and "***" in the figure indicate statistically significant differences (p<0.01 and p<0.001, respectively) compared to the results at 0 hours. [Figure 6]This figure shows the results of analyzing the expression levels of five antiviral factors (IFN-β [Figure 6A], Mx1 [Figure 6B], OAS1 [Figure 6C], RNaseL [Figure 6D], and PKR [Figure 6E]) in PIE cell lines stimulated with strain #35 ("#35" in the figure) or strain #58 ("#58" in the figure) before stimulation with Poly I:C. "*", "**", and "***" in the figure indicate statistically significant differences (p<0.05, p<0.01, and p<0.001) compared to the results of stimulation with Poly I:C alone ("Poly(I:C)+" in the figure). [Figure 7] Figures 7A-7C show the results of analyzing the A20 expression level (Figure 7A) and Tollip expression level (Figures 7B and C) in PIE cell lines stimulated with strain #35 ("#35" in the figure) or strain #58 ("#58" in the figure) before stimulation with Poly I:C for 6 hours, 3 hours, and 12 hours, respectively. "**" and "***" in the figure indicate statistically significant differences (p<0.01 and p<0.001) compared to the results of stimulation with PolyI:C alone ("Poly(I:C)+" in the figure). [Figure 8] Figure 8A shows fluorescence images of PIE cell lines analyzed by indirect immunofluorescence using anti-rotavirus antibodies, either stimulated with strain #35 (labeled "#35" in the figure) or strain #58 (labeled "#58" in the figure) before incubation with activated rotavirus solution, or not stimulated with these strains (labeled "control" in the figure). Figure 8B shows the results of analyzing the percentage of rotavirus-infected cells based on the results of Figure 8A. The percentage of rotavirus-infected cells is shown as a relative value with the control set to 100. "*" and "**" in the figure indicate a statistically significant difference (p<0.05 and p<0.01) compared to the control, respectively. [Figure 9]This figure shows the results of analyzing the expression levels of four antiviral factors (IFN-β [Figure 9A], IFN-λ [Figure 9B], Mx1 [Figure 9C], and RNaseL [Figure 9D]) in PIE cell lines stimulated with strain #35 ("#35" in the figure) or strain #58 ("#58" in the figure) before incubation in activated rotavirus solution for 3 hours, 6 hours, or 12 hours, or in PIE cell lines that were not stimulated with these strains ("control" in the figure). The expression levels of these antiviral factors are shown as relative values ​​with the control set to 1. "*", "**", and "***" in the figure indicate statistically significant differences compared to the control (p<0.05, p<0.01, and p<0.001), respectively. [Figure 10] Figure 10A shows the results of analyzing A20 expression levels in PIE cell lines stimulated with strain #35 ("#35" in the figure) or strain #58 ("#58" in the figure) before incubation in activated rotavirus solution for 3 hours or 6 hours, or in cases where stimulation with these strains was not performed ("control" in the figure). Figure 10B shows the results of analyzing Tollip expression levels in PIE cell lines stimulated with strain #35 ("#35" in the figure) or strain #58 ("#58" in the figure) before incubation in activated rotavirus solution for 3 hours, 6 hours, or 12 hours, or in cases where stimulation with these strains was not performed ("control" in the figure). A20 expression levels and Tollip expression levels are shown as relative values ​​with the control set to 1. In the figures, "*", "**", and "***" indicate statistically significant differences compared to the control group (p<0.05, p<0.01, and p<0.001, respectively). [Figure 11]Figure 11A shows the results of an analysis of the percentage of rotavirus-infected cells when PIE cell lines were incubated with activated rotavirus solution alone ("Virus" in the figure) or with activated rotavirus solution and ETEC-containing solution ("Virus + ETEC" in the figure). The percentage of rotavirus-infected cells is shown as a relative value with "Virus + ETEC" set to 100. Figure 11B shows the results of an analysis of the percentage of rotavirus-infected cells in PIE cell lines that were stimulated with strain #35 ("#35" in the figure) or strain #58 ("#58" in the figure) before incubation with activated rotavirus solution and ETEC-containing solution, or those that were not stimulated with these strains ("Control" in the figure). The percentage of rotavirus-infected cells is shown as a relative value with the control set to 100. "***" in the figure indicates a statistically significant difference (p<0.001). [Figure 12] This figure shows the results of analyzing the expression levels of three antiviral factors (IFN-β [Figure 12A], IFN-λ [Figure 12B], and Mx1 [Figure 12C]) in PIE cell lines stimulated with strain #35 ("#35" in the figure) or strain #58 ("#58" in the figure) before incubation with activated rotavirus solution and ETEC-containing solution for 3 hours, 6 hours, or 12 hours, or in PIE cell lines that were not stimulated with these strains ("control" in the figure). The expression levels of these antiviral factors are shown as relative values ​​with the control set to 1. "*", "**", and "***" in the figure indicate statistically significant differences compared to the control (p<0.05, p<0.01, and p<0.001), respectively. [Figure 13]This figure shows the results of analyzing the expression levels of three antiviral factors (RNaseL [Figure 13A], PKR [Figure 13B], and RIG-1 [Figure 13C]) in PIE cell lines stimulated with strain #35 ("#35" in the figure) or strain #58 ("#58" in the figure) before incubation with activated rotavirus solution and ETEC-containing solution for 3 hours, 6 hours, or 12 hours, or in PIE cell lines that were not stimulated with these strains ("control" in the figure). The expression levels of these antiviral factors are shown as relative values ​​with the control set to 1. "*", "**", and "***" in the figure indicate statistically significant differences compared to the control (p<0.05, p<0.01, and p<0.001), respectively. [Figure 14] Figure 14A shows the results of analyzing A20 expression levels in PIE cell lines stimulated with strain #35 ("#35" in the figure) or strain #58 ("#58" in the figure) before incubation with activated rotavirus solution and ETEC-containing solution for 3 hours or 6 hours, or in cases where stimulation with these strains was not performed ("control" in the figure). Figure 14B shows the results of analyzing Tollip expression levels in PIE cell lines stimulated with strain #35 ("#35" in the figure) or strain #58 ("#58" in the figure) before incubation with activated rotavirus solution and ETEC-containing solution for 3 hours, 6 hours, or 12 hours, or in cases where stimulation with these strains was not performed ("control" in the figure). A20 expression levels and Tollip expression levels are shown as relative values ​​with the control set to 1. In the figures, "*", "**", and "***" indicate statistically significant differences compared to the control group (p<0.05, p<0.01, and p<0.001, respectively). [Figure 15] This figure shows the results of measuring the number of colonies and the pH of the culture medium when strain #131 (labeled "#131" in the figure) or strain #71 (labeled "#71" in the figure) was cultured in wakame seaweed component-prepared agar medium. [Figure 16]The figure (right graph) shows the results of analyzing the expression levels of the antiviral factor (IFN-β) in PIE cell lines stimulated with strain #131 before stimulation with Poly I:C. The asterisk (*) in the figure indicates a statistically significant difference (p<0.05) compared to the results of stimulation with Poly I:C alone (left graph). [Figure 17] This figure shows the results of analyzing NSP5 expression levels in PIE1-3 cell lines stimulated with seven types of Lactobacillus bacterial strains (#16 [labeled "#16" in the figure], #6VG132 [labeled "#6VG132" in the figure], #6ML6109 [labeled "#6ML6109" in the figure], #6ML686 [labeled "#6ML686" in the figure], #3CS123 [labeled "#3CS123" in the figure], #6VG141 [labeled "#6VG141" in the figure], and #2CS82 [labeled "#2CS82" in the figure]) before incubation with activated rotavirus solution, or in PIE1-3 cell lines that were not stimulated with these strains (labeled "control" in the figure). In the figure, "**" and "***" indicate statistically significant differences compared to the control (p<0.01 and p<0.001, respectively). [Figure 18] This figure shows the results of an analysis of the percentage of rotavirus-infected cells in PIE1-3 cell lines that were stimulated with two types of Lactobacillus bacterial strains (the #1FeB18 strain [labeled "#1FeB18" in the figure] and the #4FeB195 strain [labeled "#4FeB195" in the figure]) before incubation with activated rotavirus solution, or in cells that were not stimulated with these strains (labeled "control" in the figure). The percentage of rotavirus-infected cells is shown as a relative value with the control set to 1. An asterisk (*) in the figure indicates a statistically significant difference compared to the control (p<0.05). [Modes for carrying out the invention] 【0011】 The antiviral agent of the present invention is an agent (hereinafter sometimes referred to as "the antiviral agent") that contains one or more Lactobacillus bacterial strains (i.e., Lactobacillus bacterial strains having a 16S rRNA gene that is at least 90% identical to the nucleotide sequence shown in Sequence ID No. 1, and that have an effect of enhancing the expression of antiviral factors and / or reducing the expression of downregulatory factors of antiviral factors) that are specified for the use "for antiviral purposes". Here, the 16S rRNA gene is usually contained in the genomic DNA of the Lactobacillus bacterial strains. 【0012】 The antiviral agent in question may be used alone as livestock feed, food and beverages, or pharmaceuticals (formulations) containing the Lactobacillus bacterial strain, which is an antiviral probiotic. It may also be mixed with additives and used in the form of a composition (livestock feed composition, food and beverage composition, or pharmaceutical composition). Examples of the food and beverages mentioned above include health foods (functional foods, nutritional supplements, health supplements, fortified foods, nutritional adjustment foods, supplements, etc.) and health functional foods (foods for specified health uses, nutrient function foods, foods with functional claims, etc.). The antiviral agent in question is preferably used as livestock feed or food and beverages. 【0013】 In this specification, "antiviral" means preventing and / or improving (treating) viral infections by actions such as suppressing viral replication, inactivating viruses, or reducing susceptibility to viruses. 【0014】 The above-mentioned antiviral factors can be any factors that cause antiviral activity in mammalian cells (e.g., polypeptides, proteins [specifically cytokines, antibodies], polynucleotides, sugars, lipids), and examples include interferon (IFN)-α, IFN-β, IFN-λ, Mx1 (MX dynamin like GTPase 1), OAS1 (2'-5'-oligoadenylate synthetase 1), RNaseL, PKR (Protein kinase R), RIG-I (Retinoic acid inducible gene-I), ISG15 (IFN stimulated gene 15kDa), MDA5 (Melanoma differentiation-associated gene 5), IPS-1 (Interferon-β promoter stimulator-1), etc. Since their effects have been demonstrated in the embodiment described later, one or more antiviral factors selected from IFN-β, IFN-λ, Mx1, OAS1, RNaseL, PKR, and RIG-I can be suitably exemplified. 【0015】 The above-mentioned "downregulatory factors for antiviral factors" can be any factor that causes a decrease in the expression of antiviral factors (e.g., polypeptides, proteins, polynucleotides, sugars, lipids), for example, A20 (also known as TNFAIP3 [Tumor Necrosis Factor Alpha-Induced Protein 3]), Tollip (Toll-interacting protein), RNF125 (Ring Finger Protein 125), DUBA (Deubiquitinase A), CYLD (CYLD Lysine 63 Deubiquitinase), etc. Since their effects have been demonstrated in the embodiment described later, one or two downregulatory factors for antiviral factors selected from A20 and Tollip can be suitably exemplified. 【0016】 The Lactobacillus bacterial strain in question can be characterized by its enhanced expression of one or more receptors selected from TLR (Toll-like receptor) 2, TLR4, and NOD2 (Nucleotide binding oligomerization domain-like receptor 2) (hereinafter sometimes referred to as "antiviral factor receptors"). 【0017】 In this specification, the expression of antiviral factors, downregulatory factors of antiviral factors, and antiviral factor receptors (hereinafter collectively referred to as "antiviral factors, etc.") means the expression of antiviral factors, etc. themselves, and / or the expression of the transcript (specifically, mRNA) of the gene encoding the antiviral factors, etc. (i.e., antiviral factor, etc. gene). The expression level of antiviral factors, etc. can be detected using methods such as Western blotting, indirect immunofluorescence assay, flow cytometry, ELISA, EIA, and RIA. Furthermore, the expression level of the transcript of the antiviral factor, etc. gene can be detected by directly detecting the mRNA of the antiviral factor, etc. gene, or by indirectly detecting cDNA synthesized using the mRNA of the antiviral factor, etc. gene as a template. Examples of methods for detecting the mRNA of the antiviral factor, etc. gene include (Reverse Transcription)-PCR, Northern blotting, microarray, and ISH. Furthermore, methods for detecting cDNA synthesized using mRNA of antiviral factor genes as a template include, for example, the LAMP method, PCR method (e.g., real-time PCR method [intercalator method, 5'-nuclease method, cycling probe method, etc.], ddPCR method), LCR method, sequencing method using next-generation sequencers, Southern hybridization method, microarray method, ISH method, etc., using the cDNA detection probes described in this case. 【0018】 In this specification, "enhanced expression of antiviral factors," "decreased expression of downregulatory factors of antiviral factors," and "enhanced expression of antiviral factor receptors" mean, respectively, that when a mammalian cell line is cultured in the presence of the Lactobacillus bacterial strain, compared to a control group where the mammalian cell line is cultured in the absence of the Lactobacillus bacterial strain, "the expression level of antiviral factors increases," "the expression level of downregulatory factors of antiviral factors decreases," and "the expression level of antiviral factor receptors increases." The mammalian cell line may be stimulated with the target virus of the antiviral agent, a substance that induces pseudoviral infection (e.g., Polyinosinic-polycytidylic acid [Poly I:C]), and / or pathogenic bacteria before or after culturing in the presence or absence of the Lactobacillus bacterial strain. Whether the expression level of antiviral factors, etc., has increased or decreased can be determined by setting an arbitrary threshold (cutoff value). Examples of such thresholds include the mean value of the expression level of antiviral factors, etc., in the control group; mean value + standard deviation (SD); mean value + 2SD; mean value + 3SD; median; interquartile range, etc. Furthermore, the threshold can also be calculated using a Receiver Operating Characteristic (ROC) curve with statistical analysis software, based on expression level data when mammalian cell lines are cultured in the presence of the Lactobacillus bacterial strain in question and expression level data when mammalian cell lines are cultured in the absence of the Lactobacillus bacterial strain in question, so as to maximize sensitivity (the proportion of mammalian cell lines cultured in the presence of the Lactobacillus bacterial strain in question that can be correctly identified as positive) and specificity (the proportion of mammalian cell lines cultured in the absence of the Lactobacillus bacterial strain in question that can be correctly identified as negative). 【0019】 Examples of the mammalian cell lines mentioned above include human intestinal epithelial cell lines (Caco-2), porcine intestinal epithelial cell lines (PIE [Porcine Intestinal Epitheliocyte] cell lines), and bovine intestinal epithelial cell lines (BIE [Bovine Intestinal Epitheliocyte] cell lines). 【0020】 The target viruses of this antiviral agent are not particularly limited, and examples include DNA viruses (double-stranded DNA viruses, single-stranded DNA viruses, etc.), RNA viruses (double-stranded RNA viruses, single-stranded RNA(+) viruses, single-stranded RNA(-) viruses, etc.). In the embodiment described later, the effect on double-stranded RNA model viruses has been demonstrated, so double-stranded RNA viruses are preferred. More specifically, target viruses include influenza virus (single-stranded RNA(-) virus), norovirus (single-stranded RNA(+) virus), rotavirus (double-stranded RNA virus), rubella virus (single-stranded RNA(+) virus), measles virus (single-stranded RNA(+) virus), RSV (single-stranded RNA(-) virus), herpesvirus (double-stranded DNA virus), hepatitis A virus (single-stranded RNA(+) virus), hepatitis B virus (double-stranded DNA virus), Examples of viruses that can be used include hepatitis C virus (single-stranded RNA(+) virus), hepatitis E virus (single-stranded RNA(+) virus), adenovirus (double-stranded DNA virus), foot-and-mouth disease virus (single-stranded RNA(+) virus), rabies virus (single-stranded RNA(-) virus), human immunodeficiency virus (single-stranded RNA(+) virus), and coronavirus (single-stranded RNA(+) virus). In the embodiment described later, the effectiveness of rotavirus has been demonstrated, so it can be preferably used as an example. Influenza viruses include types A, B, and C, avian influenza viruses and their various subtypes, and coronaviruses include not only common coronaviruses that cause the common cold, but also novel coronaviruses (e.g., severe acute respiratory syndrome coronavirus [SARS and SARS-CoV-2], Middle East respiratory syndrome coronavirus [MERS], and COVID-19). 【0021】 The antiviral agent can be applied to any mammal that requires prevention and / or improvement (treatment) of a viral infection. As demonstrated in the embodiment described later, it effectively exhibits antiviral effects even in cases of combined viral and pathogenic bacterial infections. Therefore, mammals that require prevention and / or improvement (treatment) of viral infections in cases of combined viral and pathogenic bacterial infections can be suitably exemplified. 【0022】 In this specification, examples of pathogenic bacteria include Mycoplasma, diarrheagenic Escherichia coli (e.g., enteropathogenic Escherichia coli [EPEC], enteroinvasive Escherichia coli [EIEC], enterotoxigenic Escherichia coli [ETEC], enteroaggregative and adherent Escherichia coli [EAggEC], enterohemorrhagic Escherichia coli [EHEC]), and Streptococcus. 【0023】 In this specification, mammals can include humans and non-human mammals (e.g., monkeys, mice, rats, dogs, cats, livestock [e.g., rabbits, pigs, horses, cattle, sheep, goats, deer]), and humans and livestock can be preferred examples. 【0024】 The Lactobacillus bacterial strain in question may be a living or dead bacterial strain, as long as it possesses a 16S rRNA gene that is at least 90% identical to the nucleotide sequence of Sequence ID No. 1, and has an effect of enhancing the expression of antiviral factors and / or reducing the expression of downregulatory factors for antiviral factors. The Lactobacillus bacterial strains in this case include Lactobacillus salivarius strains or Lactobacillus plantarum strains whose effects have been demonstrated in the embodiment described later, as well as Lactobacillus bacterial strains that, although of a different species from Lactobacillus salivarius strains or Lactobacillus plantarum strains (for example, Lactobacillus hayakitensis, Lactobacillus agilis, Lactobacillus aviarius subsp. araffinosus, Lactobacillus aviarius subsp. aviarius), possess a 16S rRNA gene that is at least 90% identical to the nucleotide sequence of Sequence ID No. 1, and that have an effect of enhancing the expression of antiviral factors and / or reducing the expression of downregulatory factors of antiviral factors. Specifically, the Lactobacillus bacterial strain in question is from an international depositary. Entrustment Number NITE B Lactobacillus salivarius strain (this case #35), deposited as P-03218; international deposit Entrustment Number NITE B Lactobacillus salivarius strain (strain #58 in this case), deposited as P-03219; international deposit Entrustment Number NITE B Lactobacillus salivarius strain deposited as P-03221 (strain #131 in this case); and international depositary Entrustment Number NITE B Lactobacillus salivarius strain (strain #71 in this case) deposited as P-03220; and international depositary Entrustment Number NITE BLactobacillus plantarum strain (strain #16 in this case), deposited as P-03474; international deposit Entrustment Number NITE B Lactobacillus plantarum strain (this case #6VG132 strain) deposited as P-03467; international deposit Entrustment Number NITE B Lactobacillus plantarum strain (this case #6ML6109 strain) deposited as P-03468; international deposit Entrustment Number NITE B Lactobacillus plantarum strain deposited as P-03466 (this case #6ML686 strain); international deposit Entrustment Number NITE B Lactobacillus plantarum strain (this case #3CS123 strain) deposited as P-03471; international deposit Entrustment Number NITE B Lactobacillus plantarum strain (this case #6VG141 strain) deposited as P-03469; international deposit Entrustment Number NITE B Lactobacillus plantarum strain (this case #2CS82 strain) deposited as P-03470; international deposit Entrustment Number NITE B Lactobacillus plantarum strain deposited as P-03472 (this case #1FeB18 strain); and international depositary Entrustment Number NITE B Lactobacillus deposited as P-03473. Mucosae The strain (this case #4FeB195 strain) can be cited, and since its antiviral effect has been demonstrated in this embodiment described later, it is accepted as an international depositary. Entrustment Number NITE B Lactobacillus salivarius strain (this case #35), deposited as P-03218; international deposit Entrustment Number NITE B Lactobacillus salivarius strain (strain #58 in this case), deposited as P-03219; international deposit Entrustment Number NITE B Lactobacillus salivarius strain (this case #131 strain), deposited as P-03221; international deposit EntrustmentNumber NITE B Lactobacillus plantarum strain (strain #16 in this case), deposited as P-03474; international deposit Entrustment Number NITE B Lactobacillus plantarum strain (this case #6VG132 strain) deposited as P-03467; international deposit Entrustment Number NITE B Lactobacillus plantarum strain (this case #6ML6109 strain) deposited as P-03468; international deposit Entrustment Number NITE B Lactobacillus plantarum strain deposited as P-03466 (this case #6ML686 strain); international deposit Entrustment Number NITE B Lactobacillus plantarum strain (this case #3CS123 strain) deposited as P-03471; international deposit Entrustment Number NITE B Lactobacillus plantarum strain (this case #6VG141 strain) deposited as P-03469; international deposit Entrustment Number NITE B Lactobacillus plantarum strain (this case #2CS82 strain) deposited as P-03470; international deposit Entrustment Number NITE B Lactobacillus plantarum strain deposited as P-03472 (this case #1FeB18 strain); and international depositary Entrustment Number NITE B Lactobacillus deposited as P-03473. Mucosae One or more strains selected from the strains (this case #4FeB195 strain) can be suitably exemplified. 【0025】 In the present invention, "at least 90% identity with the nucleotide sequence shown in SEQ ID NO: 1" means that one or several nucleotides in the nucleotide sequence of SEQ ID NO: 1 are substituted, deleted, inserted, added, or inverted, and that 90% or more of the entire nucleotide sequence of SEQ ID NO: 1 is identical. Here, "nucleotide sequence in which one or several nucleotides are substituted, deleted, inserted, added, or inverted" means, for example, a nucleotide sequence in which a number of nucleotides within the range of 1 to 149, preferably 1 to 100, more preferably 1 to 75, even more preferably 1 to 50, even more preferably 1 to 40, even more preferably 1 to 30, and even more preferably 1 to 15 are substituted, deleted, inserted, added, or inverted. 【0026】 In the present invention, "at least 90% identity" is preferably 91% or more, more preferably 92% or more, even more preferably 93% or more, even more preferably 94% or more, particularly preferably 95% or more, particularly more preferably 96% or more, particularly even more preferably 97% or more, particularly even more preferably 98% or more, and most preferably 99% or more (about 100%) identity. The identity of nucleotide sequences can be determined using a program called BLASTN (Altschul SF, et al: J Mol Biol 215: 403, 1990), which is based on a program called BLASTX or BLASTP (Altschul SF, et al: J Mol Biol 215: 403, 1990), which is based on the BLAST algorithm by Carlin and Arthur (Proc. Natl. Acad. Sci. USA 87:2264-2268, 1990, Proc Natl Acad Sci USA 90: 5873, 1993), which is based on a program called BLASTN (Altschul SF, et al: J Mol Biol 215: 403, 1990). When analyzing nucleotide sequences using BLASTN, the parameters are, for example, score=100 and word length=12. 【0027】 The Lactobacillus bacterial strains in question also include those that possess the ability to utilize wakame seaweed. Here, "wakame seaweed utilization" refers to the ability to synthesize substances necessary for Lactobacillus bacteria, such as proteins, nucleic acids, sugars, and lipids, using wakame seaweed as a carbon or nitrogen source. 【0028】 The antiviral agent in question is broadly classified into liquid and non-liquid types. The liquid type of the antiviral agent can be manufactured by purifying the culture medium of the Lactobacillus bacterial strain in question, adding appropriate physiological saline or replacement fluid or pharmaceutical additives as needed, and filling it into ampoules or vials. On the other hand, the non-liquid type of the antiviral agent can be manufactured by adding an appropriate cryoprotective agent (e.g., glycerol, dimethyl sulfoxide [DMSO], trehalose, dextran) to the liquid type of the antiviral agent, filling it into ampoules or vials, and then freezing or freeze-drying it. 【0029】 The antiviral agent in question can be administered either orally or parenterally. Examples of parenteral administration include intravenous administration and local administration. 【0030】 In this specification, examples of additives include pharmaceutically acceptable conventional carriers, binders, stabilizers, excipients, diluents, pH buffers, disintegrants, isotonic agents, additives, coatings, solubilizers, lubricants, gliding agents, solubilizers, flavoring agents, sweeteners, solvents, gelling agents, and nutrients. Specific examples of such additives include water, wakame seaweed components, physiological saline, animal fats and oils, vegetable oils, lactose, starch, gelatin, crystalline cellulose, gum, talc, magnesium stearate, hydroxypropylcellulose, polyalkylene glycol, polyvinyl alcohol, and glycerin. If the Lactobacillus bacterial strain in question is capable of assimilating wakame seaweed, the antiviral agent in question may preferably contain wakame components (prebiotics), which are a nutrient source for the Lactobacillus bacterial strain, as an additive, and may contain the Lactobacillus bacterial strain (preferably an antiviral immunobiotic) and an immunosinbiotic mediated by the prebiotics. The wakame components may be wakame powder obtained by crushing dried wakame seaweed, or a wakame component extract obtained by further extracting such wakame powder with water or the like. 【0031】 The appropriate dosage of the Lactobacillus bacterial strain contained in this antiviral agent cannot be determined definitively, as it varies depending on the sex, age, weight, and physical condition of the target animal (mammal). However, for example, 10 per kg of body weight per day. 4 ~10 12 cfu (Colony Forming Unit), preferably 10 6 ~10 10 It is a cfu. This amount may be administered in one dose or in several doses. Furthermore, if the antiviral agent is a livestock feed composition, the amount of Lactobacillus bacterial strain contained in the livestock feed composition is, for example, 10 per gram of livestock feed composition. 4 ~10 12 cfu / g, preferably 10 6 ~10 10 It is a CFU. 【0032】 Hereinafter, the present invention will be described more specifically by way of examples. However, the technical scope of the present invention is not limited to these examples. Unless otherwise specified, special grade or first grade reagents manufactured by Wako Pure Chemical Industries, Ltd. were used for the reagents, and Milli-Q grade water was used for all water. 【Example】 【0033】 Example 1. Search for antiviral factors Search was conducted for factors serving as indicators for evaluating the antiviral properties of probiotics. 【0034】 1-1 Materials and methods 【0035】 [Test cells] For the PIE cell line, cells cloned from the small intestine of newborn pigs of a three-way cross (LWD; landrace×large white×durock) were used. 【0036】 [Cell culture] The PIE cell line was cultured in DMEM liquid medium (high glucose, containing L-glutamine and sodium pyruvate; manufactured by GIBCO) (hereinafter simply referred to as "DMEM liquid medium") containing 10% FCS (fetal bovine serum) and 1% streptomycin / penicillin using a 250 mL flask (manufactured by Sumitomo Bakelite Co., Ltd.) coated with type I collagen. When confluent was reached, it was washed twice with PBS and incubated at 37°C for 5 minutes in epithelial buffer (PBS solution containing 0.1 M disodium hydrogen phosphate dodecahydrate, 0.45 M sucrose, 0.36% EDTA-4Na, and 0.1% BSA). After removing the epithelial buffer, it was incubated at 37°C for 5 minutes in PBS containing 0.25% trypsin and 0.02% EDTA. DMEM liquid medium was added, the detached cells were collected, and then centrifuged (12,000 rpm × 5 minutes) to remove the culture supernatant. Fresh DMEM liquid medium was added to collect the cells. After measuring the cell count, 1×10 per flask 6Cells were seeded to form cells. After 24 hours of incubation, the culture supernatant was removed by aspirator, and new DMEM liquid medium was added for further incubation. The cells were stored at -80°C for each generation using Cellbanker (registered trademark) (manufactured by Nippon Zenyaku Kogyo Co., Ltd.). Cell culture was performed under 5% CO2 / 20% O2 and 37°C conditions. 【0037】 [Analysis of cytokine-related factor expression in PIE cell lines stimulated with Poly I:C] PIE cell lines were stimulated with Poly I:C, a double-stranded RNA virus model that induces pseudoviral infection, and the expression of cytokine-related factors was analyzed. Specifically, the analysis was performed according to the following steps [1] to [5]. [1] Place the PIE cell line in a 12-well plate coated with type I collagen (Sumitomo Bakelite Co., Ltd.) in a 3 × 10⁶ 4 Seeds were seeded to achieve a cell / well density and cultured in DMEM liquid medium for 5 days. [2] The culture medium was replaced with DMEM liquid medium containing 50 ng / mL of Poly I:C (catalog number P9582, SIGMA), and the cells were cultured for 0, 3, 6, and 12 hours to stimulate them with Poly I:C. As a control without Poly I:C stimulation, PIE cell lines were cultured in the same manner in DMEM liquid medium without Poly I:C. [3] After removing the culture medium, the cells were washed once with PBS, and total RNA was obtained from the cells according to standard procedures using cell lysate (TRIzol reagent [Invitrogen]). The concentration and purity of the RNA were measured using a NanoDrop ND-1000 spectrophotometer (Thermo Fisher Scientific). [4] cDNA was synthesized from the obtained total RNA using the Prime Script RT reagent Kit with gDNA Eraser (Perfect Real Time) (Takara Corporation) according to the protocol provided with the product. [5] Using the synthesized cDNA as a template, quantitative PCR analysis was performed using the primer set (sense primers and antisense primers) shown in Table 1 below, Platinum SYBR Green qPCR Super Mix-UDG with ROX (Invitrogen), and ABI PRISM 7300 real-time PCR system (Applied Biosystems) to analyze the mRNA expression levels of 24 cytokine-related factors (IFN-β, IFN-λ, Mx1, OAS1, RNaseL, PKR, RIG-I, TLR2, TLR3, TLR4, NOD1, NOD2, MCP-1 [also known as CCL2], IL-6, IL-8 [also known as CXCL8], IL-12, IL-18, TNFα, A20, BCL-3, Tollip, IRAK-M, MKP-1, and SIGIRR) and the β-actin gene, according to the protocol provided with the product. The expression levels of various cytokine-related factors induced by Poly I:C stimulation were calculated based on the formula (expression level of mRNA of various cytokine-related factor genes / expression level of mRNA of β-actin gene induced by PolyI:C stimulation) / expression level of mRNA of various cytokine-related factor genes / expression level of mRNA of β-actin gene induced by PolyI:C unstimulated). 【0038】 [Table 1] 【0039】 1-2 Results [Analysis of cytokine-related factor expression in Poly I:C-stimulated PIE cell lines] Analysis of mRNA expression levels of the 24 cytokine-related factor genes in PIE cell lines stimulated with Poly I:C revealed that the expression levels of two antiviral factors (IFN-β and Mx1) significantly increased after 3 hours post-Poly I:C stimulation. In particular, IFN-β expression levels were highest at 3 hours post-Poly I:C stimulation, while Mx1 expression levels were highest at 12 hours post-Poly I:C stimulation (see Figures 1A and 1B). 【0040】 Based on these results, we decided to use the expression level of IFN-β at 3 hours after Poly I:C stimulation and the expression level of Mx1 at 12 hours after Poly I:C stimulation as indicators for selecting the Lactobacillus bacterial strains in this study. 【0041】 Example 2. Selection of Lactobacillus bacterial strains based on antiviral activity. The Lactobacillus bacterial strains in question were selected based on the expression levels of two antiviral factors (IFN-β and Mx1). 【0042】 2-1 Method 【0043】 [Preparation of a solution containing Lactobacillus salivarius] 116 Lactobacillus salivarius strains isolated from pig intestinal tracts were inoculated into MRS liquid medium (Difco), incubated at 37°C for 16 hours, subcultured three times, and washed with PBS. After heat sterilization at 72°C for 1.5 hours, washed twice with PBS, and then transferred to DMEM liquid medium in 2.5 × 10⁶ units. 9 The cells were resuspended to a concentration of cells / mL to prepare a solution containing 116 different Lactobacillus salivarius strains. 【0044】 [Selection of Lactobacillus bacterial strains in this case] PIE cell lines were stimulated with a solution containing 116 prepared Lactobacillus salivarius strains, followed by stimulation with Poly I:C. The Lactobacillus bacterial strains in question were selected based on the expression levels of two antiviral factors (IFN-β and Mx1). Specifically, the analysis was performed according to the following procedures [1] to [4]. [1] Place the PIE cell line in a 12-well plate coated with type I collagen (Sumitomo Bakelite Co., Ltd.) in a 3 × 10⁶ 4 Seeds were seeded to achieve a cell / well density and cultured in DMEM liquid medium for 3 days. [2] Prepared solutions containing 116 different Lactobacillus salivarius strains, each in a quantity of 5.0 × 10⁶ per well. 7The cells were added to the culture medium to a concentration of cells / mL and cultured (stimulated) for 2 days. As a control of unstimulated Lactobacillus salivarius cells, PIE cells were cultured in the same manner in DMEM liquid medium without Lactobacillus salivarius cells. [3] Remove the culture medium, wash the cells twice with PBS, and then replace it with DMEM liquid medium containing 50 ng / mL Poly I:C (catalog number P9582, SIGMA), and incubate for 3 hours and 12 hours. Poly I:C stimulation was performed by culturing the cells. As a control without Poly I:C stimulation, PIE cell lines were cultured in the same manner in DMEM liquid medium without Poly I:C. [4] After removing the culture medium, the procedure from the recovery of total RNA in the cells to the analysis of the mRNA expression levels of two antiviral factor genes (IFN-β and Mx1) was carried out according to steps [3] to [5] in the section [Analysis of cytokine-related factor expression in PIE cell lines stimulated with Poly I:C] of Example 1 above. The IFN-β expression levels and Mx1 expression levels stimulated by various Lactobacillus salivarius strains were calculated based on the formula ([IFN-β gene or Mx1 gene mRNA expression level / β-actin gene mRNA expression level] when stimulated with various Lactobacillus salivarius strains before stimulation with Poly I:C) / [IFN-β gene or Mx1 gene mRNA expression level / β-actin gene mRNA expression level] when stimulated with Poly I:C) (see vertical axis in Figure 2). 【0045】 2-2 Results Analysis of the expression levels of two antiviral factors (IFN-β and Mx1) in PIE cell lines stimulated with 116 different Lactobacillus salivarius strains before stimulation with Poly I:C revealed that the highest expression levels were observed when stimulated with Lactobacillus salivarius strain #35 (hereinafter referred to as "strain #35") and Lactobacillus salivarius strain #58 (hereinafter referred to as "strain #58") (see arrows and arrowheads in Figure 2). Based on these results, strains #35 and #58 were selected as the Lactobacillus bacterial strains in question. 【0046】 1) Strain #35 is a Lactobacillus salivarius strain possessing a 16S rRNA gene consisting of the nucleotide sequence of Sequence ID No. 1, and has the following characteristics. Furthermore, strain #35 was internationally deposited with the National Institute of Technology and Evaluation (NITE) Patent Microorganisms Depositary (NPMD) on May 19, 2020 (Address: Room 122, 2-5-8 Kazusakamatari, Kisarazu-shi, Chiba 292-0818, Japan). Entrustment Number NITE B It is deposited internationally as P-03218. (a) Cell morphology Shape: Rod-shaped bacterium, Spore formation: (-), Motility: (-) (b) Colony morphology (The morphology of colonies cultured aerobically on MRS agar medium at 37°C for 24 hours was observed.) (1) Gram staining: (+) (2) Gas production: (-) (3) Catalase activity: (-) (4) Indole origin: (-) (5) Attitude towards oxygen: facultative anaerobic (6) Optimum growth temperature: 37~40℃ (7) Optimal growth pH: pH5.5~5.8 2) Strain #58 is a Lactobacillus salivarius strain possessing a 16S rRNA gene consisting of the nucleotide sequence of Sequence ID No. 1, and has the following characteristics. Furthermore, strain #58 was internationally deposited with the National Institute of Technology and Evaluation (NITE) Patent Microorganism Depositary Center (NPMD) (Address: Room 122, 2-5-8 Kazusa Kamatari, Kisarazu City, Chiba Prefecture 292-0818, Japan) on May 19, 2020. Entrustment Number NITE BIt is deposited internationally as P-03219. (a) Cell morphology Shape: Rod-shaped bacterium, Spore formation: (-), Motility: (-) (b) Colony morphology (The morphology of colonies cultured aerobically on MRS agar medium at 37°C for 24 hours was observed.) (1) Gram staining: (+) (2) Gas production: (-) (3) Catalase activity: (-) (4) Indole origin: (-) (5) Attitude towards oxygen: facultative anaerobic (6) Optimum growth temperature: 37~40℃ (7) Optimal growth pH: pH5.5~5.8 【0047】 Example 3. Evaluation of the immunomodulatory ability of the Lactobacillus bacterial strain in question. PIE cell lines were stimulated with either the selected cell line #35 or cell line #58, and the cellular immune response was analyzed. 【0048】 3-1 Method The analysis of the cellular immune response was performed according to the following procedures [1] to [3]. [1] Place the PIE cell line in a 12-well plate coated with type I collagen (Sumitomo Bakelite Co., Ltd.) in a 3 × 10⁶ 4 Seeds were seeded to achieve a cell / well density and cultured in DMEM liquid medium for 3 days. [2] The amount of the subject stock #35 and the subject stock #58 was 5.0 × 10 per well, respectively. 7 The cells were added to the culture medium to a concentration of cells / mL and cultured for 0 hours (unstimulated), 3 hours, 6 hours, 12 hours, 24 hours, and 48 hours (stimulated). As a control for these unstimulated cell lines, PIE cell lines were cultured in the same manner in DMEM liquid medium that did not contain these cell lines. [3] After removing the culture medium, the procedure from recovering total RNA in the cells to analyzing the mRNA expression levels of five receptor genes (TLR2, TLR3, TLR4, NOD1, and NOD2) and seven antiviral factor genes (IFN-β, IFN-λ, Mx1, OAS1, RNaseL, PKR, and RIG-I) was carried out according to steps [3] to [5] in the section [Analysis of cytokine-related factor expression in PIE cell lines stimulated with Poly I:C] of Example 1 above. The expression levels of various receptors (see Figure 3) and various antiviral factors (see Figures 4 and 5) stimulated by strain #35 or strain #58 were calculated based on the formula (expression level of mRNA of various receptor genes or various antiviral factor genes stimulated by strain #35 or strain #58 / expression level of mRNA of β-actin gene) / expression level of mRNA of various receptor genes or various antiviral factor genes without stimulation of the aforementioned strain (0 hours) / expression level of mRNA of β-actin gene). 【0049】 3-2 Results Analysis of the expression levels of the five receptors in PIE cell lines stimulated with strain #35 or strain #58 revealed a significant increase in the expression levels of three receptors that recognize surface components of Gram-positive bacteria (TLR2, TLR4, and NOD2) (see Figure 3). Specifically, the expression level of TLR2 increased at 6 and 12 hours after stimulation with strain #35 and strain #58, respectively, peaking and then decreasing, while the expression levels of TLR4 and NOD2 increased for at least 48 hours after stimulation with strain #35 and strain #58 (see Figure 3). These results suggest that the cell membrane components of strains #35 and #58 in this case may be recognized as ligands by the three types of receptors mentioned above. 【0050】 Furthermore, analysis of the expression levels of the seven antiviral factors (IFN-β, IFN-λ, Mx1, OAS1, RNaseL, PKR, and RIG-I) in PIE cell lines stimulated with strain #35 or strain #58 revealed a significant increase in the expression levels of all antiviral factors, namely the two types of IFN (IFN-β and IFN-λ) and the five types of IFN-inducible factors (Mx1, OAS1, RNaseL, PKR, and RIG-I) (see Figures 4 and 5). In particular, the expression level of IFN-β increased significantly at 6 hours after stimulation with strain #35 or strain #58, and the expression level of IFN-λ increased significantly at 48 hours after stimulation with strain #35 or strain #58 (see Figure 4). 【0051】 These results indicate that strains #35 and #58 increased the expression levels of IFN and IFN-induced factors, resulting in enhanced responsiveness to viruses in PIE cell lines. In particular, since TLR3 and RIG-I are known to recognize double-stranded RNA in double-stranded RNA viruses such as rotavirus and exert antiviral activity, and Mx1 is known to inhibit the proliferation of single-stranded RNA or DNA viruses, strains #35 and #58 are expected to enhance the antiviral immune response. 【0052】 Example 4.2 Evaluation of the immunomodulatory ability of the Lactobacillus bacterial strain in question against a long-stranded RNA model virus 1 For strains #35 and #58, in order to evaluate their immunomodulatory capacity against double-stranded RNA model viruses, PIE cell lines were stimulated with either strain #35 or strain #58 before stimulation with Poly I:C, and the expression of antiviral factors was analyzed. 【0053】 4-1 Method The analysis of the cellular immune response was performed according to the following procedures [1] to [4]. [1] Place the PIE cell line in a 12-well plate coated with type I collagen (Sumitomo Bakelite Co., Ltd.) in a 3 × 10⁶ 4Seeds were seeded to achieve a cell / well density and cultured in DMEM liquid medium for 3 days. [2] The amount of the subject stock #35 and the subject stock #58 was 5.0 × 10 per well, respectively. 7 The cells were added to the culture medium to a concentration of cells / mL and cultured (stimulated) for 48 hours. As a control of these cell lines, PIE cell lines were cultured in the same manner in DMEM liquid medium that did not contain these cell lines. [3] After removing the culture medium and washing the cells twice with PBS, the medium was replaced with DMEM liquid medium containing 50 ng / mL of Poly I:C (catalog number P9582, SIGMA), and the cells were cultured for 12 hours to stimulate them with Poly I:C. As a control without Poly I:C stimulation, PIE cell lines were cultured in the same manner in DMEM liquid medium without Poly I:C. [4] After removing the culture medium, the procedure from the recovery of total RNA in the cells to the analysis of the mRNA expression levels of five antiviral factor genes (IFN-β, Mx1, OAS1, RNaseL, and PKR) was carried out according to steps [3] to [5] in the section [Analysis of cytokine-related factor expression in PIE cell lines stimulated with Poly I:C] of Example 1 above. The expression levels of various antiviral factors (see Figure 6) after stimulation of strain #35 or strain #58 were calculated based on the formula ([mRNA expression level of various antiviral factor genes / mRNA expression level of β-actin gene] when stimulated with strain #35 or strain #58 before stimulation with Poly I:C) / [mRNA expression level of various antiviral factor genes / mRNA expression level of β-actin gene] when stimulated with Poly I:C). Furthermore, for comparison, the expression levels of various antiviral factors were calculated for both the aforementioned strain and Poly I:C in an unstimulated state (see "Poly(I:C)-" in Figure 6). 【0054】 4-2 Results Prior to stimulation with Poly I:C, the expression levels of five antiviral factors (IFN-β, Mx1, OAS1, RNaseL, and PKR) in PIE cell lines stimulated with strain #35 or strain #58 were significantly increased compared to the expression levels in PIE cell lines that were not stimulated by the aforementioned strains and were stimulated with Poly I:C (see Figure 6). 【0055】 These results indicate that strain #35 or strain #58 possesses an IFN-β production-enhancing effect in response to PolyI:C stimulation and an enhancement of the expression of IFN-inducible factors (Mx1, OAS1, RNaseL, and PKR). Therefore, it is suggested that strain #35 or strain #58 may be useful against double-stranded RNA virus infections. 【0056】 Example 5.2 Evaluation of the immunomodulatory ability of the Lactobacillus bacterial strain in question against a long-stranded RNA model virus 2 A20 / TNFAIP3 is known to be a negative regulator that plays a particularly important role during viral infection, and it has been reported that rotavirus infection is significantly suppressed in cells in which A20 expression is knocked down (see reference "Vet Res. 2011 Nov 3;42:111. doi: 10.1186 / 1297-9716-42-111."). Furthermore, Tollip (Toll-interacting protein) is a negative regulator that interacts with IRAK-1 to inhibit phosphorylation and negatively regulates the signaling of TLR2 and TLR4, and has been reported to be involved in regulating the expression of IRF3 (Interferon regulatory factor 3), which is involved in the expression of IFN-β and IFN-λ (see "Fish Shellfish Immunol. 2015 Dec;47(2):807-16."). Therefore, in order to analyze the mechanism of the antiviral factor enhancement effect by strain #35 or strain #58, we performed expression analysis of A20 and Tollip, which are downregulators of antiviral factors. 【0057】 5-1 Method The analysis of the cellular immune response was performed according to the following procedures [1] to [4]. [1] Place the PIE cell line in a 12-well plate coated with type I collagen (Sumitomo Bakelite Co., Ltd.) in a 3 × 10⁶ 4 Seeds were seeded to achieve a cell / well density and cultured in DMEM liquid medium for 3 days. [2] The amount of the subject stock #35 and the subject stock #58 was 5.0 × 10 per well, respectively. 7 The cells were added to the culture medium to a concentration of cells / mL and cultured (stimulated) for 48 hours. As a control of these cell lines, PIE cell lines were cultured in the same manner in DMEM liquid medium that did not contain these cell lines. [3] After removing the culture medium and washing the cells twice with PBS, the medium was replaced with DMEM liquid medium containing 50 ng / mL of Poly I:C (catalog number P9582, SIGMA), and the cells were cultured for 3 hours, 6 hours, or 12 hours to stimulate Poly I:C. As a control without Poly I:C stimulation, PIE cell lines were cultured in the same manner in DMEM liquid medium without Poly I:C. [4] After removing the culture medium, the procedure from the recovery of total RNA in the cells to the analysis of the mRNA expression levels of the A20 gene and the Tollip gene was carried out in accordance with steps [3] to [5] of item [Analysis of cytokine-related factor expression in PIE cell lines stimulated with Poly I:C] in Example 1 above. The A20 expression level and Tollip expression level (see Figure 7) of the subject strain #35 or the subject strain #58 upon stimulation were calculated based on the formula ([mRNA expression level of the A20 gene or Tollip gene / mRNA expression level of the β-actin gene] when the subject strain #35 or the subject strain #58 was stimulated before stimulation with Poly I:C) / [mRNA expression level of the A20 gene or Tollip gene / mRNA expression level of the β-actin gene] when stimulated with Poly I:C). Furthermore, for comparison, the A20 expression levels and Tollip expression levels of both the aforementioned strain and Poly I:C in an unstimulated state were also calculated (see "Poly(I:C)-" in Figure 7). 【0058】 5-2 Results Prior to stimulation with Poly I:C, the expression levels of A20 and Tollip in PIE cell lines stimulated with strain #35 or strain #58 were significantly reduced compared to the expression levels in PIE cell lines that were not stimulated by the aforementioned strains and were stimulated with Poly I:C (see Figure 7). 【0059】 Considering the results of Example 4 above, these results indicate that when strain #35 or strain #58 is administered to cells infected with double-stranded RNA virus, the expression levels of negative regulators of antiviral factors such as A20 and Tollip decrease, and an effect of enhancing the expression of antiviral factors is exerted. 【0060】 Example 6. Confirmation of the viral infection reduction effect of the Lactobacillus bacterial strain in question. Since strains #35 and #58 were shown to enhance the antiviral immune response, rotavirus infection tests were conducted to confirm that these strains have an effect in reducing viral infection. 【0061】 6-1 Materials and Methods 【0062】 [Test virus strain] The rotavirus OSU strain, a group A virus that infects livestock and uses pigs as a host, was provided by the Animal Health Research Division of the National Agriculture and Food Research Organization. 【0063】 [Preparation of activated rotavirus solution] 200 μL of DMEM liquid medium (high glucose, containing L-glutamine and sodium pyruvate; GIBCO) containing rotavirus OSU strain was mixed with 2 μL of purified triplin (T8003-1G Type I, SIGMA) at a concentration of 1 mg / mL (final trypsin concentration 10 μg / mL). After thorough mixing, the mixture was incubated at 37°C for 30 minutes and then treated with trypsin to prepare an activated rotavirus solution. 【0064】 [Rotavirus infection test and indirect immunofluorescence assay] Rotavirus infection testing and subsequent indirect immunofluorescence assays using anti-rotavirus antibodies were performed according to the following procedures [1] to [7]. [1] Place the PIE cell line in a 96-well plate coated with type I collagen (Sumitomo Bakelite Co., Ltd.) in a 3 × 10⁶ 4 Seeds were seeded to a concentration of cells / mL and cultured in DMEM liquid medium for 8 days. [2] Cell strains #35 and #58 were added to the culture medium in such a manner that each well contained 100 MOI (multiplicity of infection), and cultured (stimulated) for 48 hours. As a control of these strains, PIE cell lines were cultured in the same manner in DMEM liquid medium that did not contain these strains. [3] The cells were washed three times with FCS-free DMEM liquid medium, and 100 μL (equivalent to 1 MOI) of the activated rotavirus solution prepared according to the method described in item [Preparation of activated rotavirus solution] above was added to each well. The cells were incubated for 16 hours under 5% CO2 / 20% O2 conditions at 37°C. [4] Remove the activated rotavirus solution, add 100 μL of 80% acetone solution at 4°C to each well, and incubate at 4°C for 20 minutes to fix the cells. [5] After removing the acetone solution and washing the cells three times with PBS, a primary antibody reaction was performed using rotavirus A antibody (anti-human RVAWa strain guinea pig serum, provided by the National Agriculture and Food Research Organization, Animal Health Research Division). Specifically, the rotavirus A antibody was diluted 800-fold with PBS, 50 μL was dispensed into each well, and incubated at 37°C for 40 minutes. [6] After washing the cells three times with PBS, a secondary antibody reaction was performed using Alexa488-labeled anti-guinea pig IgG antibody (Cat. ab150185, abcam). Specifically, this antibody was diluted 400-fold in PBS at a ratio of 1:400, 50 μL was dispensed into each well, and incubated at 37°C for 40 minutes. [7] After washing the cells three times with PBS, 50 μL of PBS containing 30% glycerin was dispensed into each well, and the fluorescence signal derived from Alexa488 was detected using a fluorescence microscope (Olympus IX70-FL) (see Figure 8A). The percentage of cells positive for this fluorescence signal, i.e., rotavirus-positive (infected) cells, was calculated (see Figure 8B). 【0065】 6-2 Results First, we confirmed that PIE cell lines incubated with activated rotavirus solution produced a fluorescent signal derived from Alexa488, i.e., rotavirus-positive cells (see controls in Figures 8A and 8B). Next, when PIE cell lines were stimulated with strain #35 and strain #58 before incubation with activated rotavirus solution, the percentage of rotavirus-positive cells was significantly reduced to 66% and 57%, respectively, compared to the unstimulated cells (see #35 and #58 in Figures 8A and 8B). 【0066】 These results indicate that strains #35 and #58 have an effect in reducing (preventing) viral infection. 【0067】 Example 7. Evaluation of the immunomodulatory capacity of the Lactobacillus strain in question during viral infection. For strains #35 and #58, in order to evaluate their immunomodulatory capacity during viral infection, PIE cell lines were stimulated with either strain #35 or strain #58, then infected with rotavirus, and the expression of antiviral factors was analyzed. 【0068】 7-1 Method Rotavirus infection testing and subsequent analysis of antiviral factor expression were performed according to the following procedures [1] to [4]. [1] Place the PIE cell line in a 96-well plate coated with type I collagen (Sumitomo Bakelite Co., Ltd.) in a 5 × 10⁶ 4 Seeds were seeded to achieve a cell / well density and cultured in DMEM liquid medium for 10 days. [2] Cell strains #35 and #58 were added to the culture medium to a total MOI of 100 per well and cultured (stimulated) for 48 hours. As a control of these strains, PIE cell lines were cultured in the same manner in DMEM liquid medium without these strains. [3] The cells were washed three times with FCS-free DMEM liquid medium, and 100 μL (equivalent to 1 MOI) of the activated rotavirus solution prepared according to the method described in item [Preparation of activated rotavirus solution] of Example 6 was added to each well. The cells were incubated for 3 hours, 6 hours, or 12 hours under 5% CO2 / 20% O2 and 37°C conditions. [4] After removing the activated rotavirus solution, the procedure from the recovery of total RNA in the cells to the analysis of mRNA expression levels of four antiviral factor genes (IFN-β, IFN-γ, Mx1, and RNaseL) was carried out according to steps [3] to [5] in the section [Analysis of cytokine-related factor expression in PIE cell lines stimulated with Poly I:C] of Example 1 above. 【0069】 7-2 Results When PIE cell lines were stimulated with strain #35 or strain #58 before incubation with activated rotavirus solution, the expression levels of four antiviral factors (IFN-β, IFN-γ, Mx1, and RNaseL) were significantly increased compared to unstimulated strains (see Figure 9). 【0070】 These results indicate that administering strains #35 and #58 to virus-infected cells enhances the expression of antiviral factors. 【0071】 Example 8. Evaluation of the immunomodulatory capacity of the Lactobacillus bacterial strain in question during viral infection. For strains #35 and #58, in order to evaluate their immunomodulatory capacity during viral infection, PIE cell lines were stimulated with either strain #35 or strain #58, then infected with rotavirus, and the expression of A20 and Tollip, which downregulate the expression of antiviral factors, was analyzed. 【0072】 8-1 Method Rotavirus infection testing and subsequent expression analysis of A20 and Tollip were performed according to the following procedures [1] to [4]. [1] Place the PIE cell line in a 96-well plate coated with type I collagen (Sumitomo Bakelite Co., Ltd.) in a 3 × 10⁶ 4 Seeds were seeded to a concentration of cells / mL and cultured in DMEM liquid medium for 8 days. [2] Cell strains #35 and #58 were added to the culture medium to a total MOI of 100 per well and cultured (stimulated) for 48 hours. As a control of these strains, PIE cell lines were cultured in the same manner in DMEM liquid medium without these strains. [3] The cells were washed three times with FCS-free DMEM liquid medium, and 100 μL (equivalent to 1 MOI) of the activated rotavirus solution prepared according to the method described in item [Preparation of activated rotavirus solution] of Example 6 was added to each well. The cells were incubated for 3 hours, 6 hours, or 12 hours under 5% CO2 / 20% O2 and 37°C conditions. [4] After removing the activated rotavirus solution, the procedure from the recovery of total RNA in the cells to the analysis of mRNA expression levels of four antiviral factor genes (IFN-β, IFN-γ, Mx1, and RNaseL) was carried out according to steps [3] to [5] in the section [Analysis of cytokine-related factor expression in PIE cell lines stimulated with Poly I:C] of Example 1 above. 【0073】 8-2 Results When PIE cell lines were stimulated with strain #35 or strain #58 before incubation with activated rotavirus solution, the expression levels of A20 and Tollip were significantly reduced compared to the unstimulated strains (see Figure 10). 【0074】 These results indicate that when strains #35 and #58 are administered to virus-infected cells, the expression levels of downregulatory factors for antiviral factors (e.g., A20 and Tollip) decrease, and the expression of antiviral factors is enhanced. 【0075】 Example 9. Confirmation of the effect of the Lactobacillus bacterial strain in this case on reducing combined rotavirus and ETEC infections. In real life, infections occur not only from viruses alone, but also from co-infections with pathogenic bacteria. Therefore, we constructed a co-infection system involving rotavirus and enterotoxigenic Escherichia coli (ETEC). First, we verified whether there was a difference in rotavirus infection efficiency between rotavirus-only infection and co-infection with rotavirus and ETEC. Next, we analyzed whether strains #35 and #58 were effective against co-infection with rotavirus and ETEC. 【0076】 9-1 Materials and Methods 【0077】 [Preparation of ETEC-containing solution] The ETEC strain (provided by the National Agriculture and Food Research Organization, Animal Health Research Division) was streaked onto agar medium containing 5% defibroused sheep blood and incubated at 37°C for 20 hours. Colonies were picked and inoculated into 5 mL of tryptone soy broth (TSB) liquid medium (manufactured by BD Japan), and re-cultivated at 37°C for 5-8 days by standing still. Subsequently, colonies were picked from the film-forming region and inoculated into 11 mL of TSB, and incubated with shaking at 37°C for 20 hours. After incubation, the cells were collected by centrifugation, washed three times with PBS, and heat-sterilized at 100°C for 15 minutes. After washing with PBS, the bacterial concentration was 1.5 × 10⁶. 10 The ETEC-containing solution was prepared by suspending the cells in DMEM liquid medium to a concentration of cells / mL. 【0078】 [Combined infection testing of rotavirus and ETEC, and indirect immunofluorescence assay] The rotavirus-ETEC combined infection test and subsequent indirect immunofluorescence assay using anti-rotavirus antibodies were performed according to the following procedures [1] to [4]. [1] Place the PIE cell line in a 96-well plate coated with type I collagen (Sumitomo Bakelite Co., Ltd.) in a 3 × 10⁶ 4 Seeds were seeded to achieve a cell / well density and cultured in DMEM liquid medium for 8 days. [2] Cell strains #35 and #58 were added to the culture medium to a total MOI of 100 per well and cultured (stimulated) for 48 hours. As a control of these strains, PIE cell lines were cultured in the same manner in DMEM liquid medium without these strains. [3] The cells were washed three times with FCS-free DMEM liquid medium, and 100 μL (equivalent to 1 MOI) of activated rotavirus solution prepared according to the method described in the section [Preparation of activated rotavirus solution] of Example 6 was added to each well. Then, 50 μL (equivalent to 1 MOI) of ETEC-containing solution prepared according to the method described in the section [Preparation of ETEC-containing solution] was added to each well, and the cells were incubated for 16 hours under 5% CO2 / 20% O2 conditions at 37°C. As a control for virus-only infection, PIE cell lines treated with activated rotavirus solution alone were incubated in the same manner. [4] After removing the activated rotavirus solution and ETEC-containing solution, the procedure from cell fixation to the indirect immunofluorescence assay was carried out according to steps [4] to [7] in the section [Rotavirus infection test and indirect immunofluorescence assay] of Example 6 above. 【0079】 9-2 Results When PIE cell lines were incubated with activated rotavirus solution and ETEC-containing solution, the proportion of rotavirus-positive cells was significantly increased compared to incubation with activated rotavirus solution alone (see Figure 11A). 【0080】 These results indicate that rotavirus-ETEC co-infection increased the rotavirus infection efficiency in PIE cell lines compared to rotavirus infection alone. 【0081】 Next, when PIE cell lines were stimulated with strain #35 or strain #58 before incubation with activated rotavirus solution and ETEC-containing solution, the proportion of rotavirus-positive cells was significantly reduced compared to when these strains were not used (see Figure 11B). 【0082】 These results indicate that strains #35 and #58 effectively exert a reduction (preventive) effect against viral infections in cases of combined viral and pathogenic bacterial infections. 【0083】 Example 10. Evaluation of the immunomodulatory capacity of the Lactobacillus bacterial strain in question during viral and bacterial infections. For strains #35 and #58, in order to evaluate their immunomodulatory capacity during viral-pathogenic bacterial co-infections, PIE cell lines were stimulated with either strain #35 or strain #58, then infected with rotavirus, and the expression of antiviral factors and downregulatory factors of antiviral factors was analyzed. 【0084】 10-1 Method The combined viral and pathogenic bacterial infection tests, and the subsequent expression analysis of antiviral factors and downregulatory factors of antiviral factors, were performed according to the following procedures [1] to [4]. [1] Place the PIE cell line in a 96-well plate coated with type I collagen (Sumitomo Bakelite Co., Ltd.) in a 5 × 10⁶ 4 Seeds were seeded to achieve a cell / well density and cultured in DMEM liquid medium for 10 days. [2] Cell strains #35 and #58 were added to the culture medium to a total MOI of 100 per well and cultured (stimulated) for 48 hours. As a control of these strains, PIE cell lines were cultured in the same manner in DMEM liquid medium without these strains. [3] The cells were washed three times with FCS-free DMEM liquid medium, and 100 μL (equivalent to 1 MOI) of activated rotavirus solution prepared according to the method described in the section [Preparation of activated rotavirus solution] of Example 6 was added to each well. Then, 50 μL (equivalent to 1 MOI) of ETEC-containing solution prepared according to the method described in the section [Preparation of ETEC-containing solution] was added to each well, and the cells were incubated for 16 hours under 5% CO2 / 20% O2 conditions at 37°C. As a control for virus-only infection, PIE cell lines treated with activated rotavirus solution alone were incubated in the same manner. [4] After removing the activated rotavirus solution and ETEC-containing solution, the procedure from recovering total RNA in the cells to analyzing the mRNA expression levels of six antiviral factor genes (IFN-β, IFN-γ, Mx1, RNaseL, PKR, and RIG-1) and the mRNA expression levels of two downregulatory factors of antiviral factors (A20 and Tollip) was carried out in accordance with steps [3] to [5] of the above Example 1 item [Analysis of cytokine-related factor expression in PIE cell lines stimulated with Poly I:C]. 【0085】 10-2 Results When PIE cell lines were stimulated with strain #35 or strain #58 before incubation with activated rotavirus solution and ETEC-containing solution, the expression levels of six antiviral factors (IFN-β, IFN-γ, Mx1, RNaseL, PKR, and RIG-1) were significantly increased compared to the unstimulated strains (see Figures 12 and 13), while the expression levels of two downregulatory factors for antiviral factors (A20 and Tollip) were significantly decreased (see Figure 14). 【0086】 These results indicate that when the Lactobacillus bacterial strains in question (strain #35 and strain #58) are administered to cells infected with a combination of viruses and pathogenic bacteria, the expression levels of downregulatory factors for antiviral factors (e.g., A20 and Tollip) decrease, and an effect of enhancing the expression of antiviral factors is exerted. 【0087】 Example 11. Selection of Lactobacillus bacterial strains based on their ability to utilize wakame seaweed. Regarding the metabolites of bacteria that utilize seaweed, organic acids produced from hydrated carbon in algae have been reported to activate intestinal microorganisms in humans and marine invertebrates (see "Front Immunol. 2014 Jan 14;4:512." and "NewPhytol. 2010 Oct;188(1):82-97."). Furthermore, in prebiotic-related research, there are reports that metabolites obtained by microbial fermentation of red algae exhibit antioxidant, anticoagulant, and immunomodulatory effects (see "Phytomedicine. 2012 Jun 15;19(8-9):797-803."). These findings indicate the existence of microorganisms that can utilize marine biological materials as substrates, and that developing and applying them will create new value. Meanwhile, in 2010, a research team led by Jan-Hendrik Hehemann identified an enzyme that decomposes algal cell walls among marine bacteria, and reported that the gene encoding this enzyme exists only in the gut bacteria of Japanese people (see "Anim Sci J. 2011 Apr;82(2):274-81."). From this report, it was hypothesized that the Japanese diet influenced gut bacteria to acquire the newly acquired ability to decompose red algal cell walls, which then spread to the gut environment and became established in the Japanese gut microbiota. This suggests that consuming seaweed leads to the emergence of gut bacteria that can actively utilize seaweed. Therefore, a large-scale analysis of the gut microbiota in the intestinal mucus of pigs administered wakame residue was conducted to analyze the composition of gut microbiota, and wakame-utilizing Lactobacillus bacterial strains were selected using wakame component-prepared agar medium. 【0088】 11-1 Materials and Methods [Preparation of liquid culture medium containing wakame seaweed components] 0.1 g of wakame powder and 100 mL of Milli-Q water were placed in a bottle and autoclaved (121°C, 15 minutes) to prepare a 0.1% wakame aqueous solution. This solution was dispensed into 50 mL tubes and centrifuged (6000 rpm, 20 minutes, 4°C). The supernatant was collected, and sodium chloride and yeast extract were added to this supernatant (wakame component) to final concentrations of 0.5% and 0.1%, respectively, to prepare a 0.1% wakame component-containing liquid culture medium. Agar was then added to this 0.1% wakame component-containing liquid culture medium to a final concentration of 1.5%, to prepare a 0.1% wakame component-containing agar culture medium. 【0089】 [Culture test of Lactobacillus salivarius strain in liquid culture medium containing wakame seaweed components] 136 Lactobacillus salivarius strains isolated from the intestinal tract were inoculated onto MRS agar. After 72 hours, each bacterial strain was placed in 5 mL of MRS liquid medium and incubated at 37°C for 24 hours. After two subculturings in 100 μL of 0.1% wakame seaweed liquid medium, the culture was adjusted with PBS to an OD of 0.5, and 5 mL of 0.1% wakame seaweed liquid medium was added. 100 μL of this medium was then inoculated onto 0.1% wakame seaweed agar, and the pH and colony count of the medium were measured every 6 hours (see Figure 15). 【0090】 11-2 Results Two Lactobacillus salivarius strains were identified that grow in a liquid culture medium containing wakame seaweed components: Lactobacillus salivarius strain #131 (sometimes referred to as "strain #131" in this specification) and Lactobacillus salivarius strain #71 (sometimes referred to as "strain #71" in this specification). 【0091】 1) Strain #131, like strains #35 and #58, is a Lactobacillus salivarius strain possessing a 16S rRNA gene consisting of the nucleotide sequence of Sequence ID No. 1, and has the same characteristics as strains #35 and #58. Specifically, strain #131 has the following characteristics. Strain #131 was internationally deposited with the National Institute of Technology and Evaluation (NITE) Patent Microorganism Depositary Center (NPMD) (Address: Room 122, 2-5-8 Kazusa Kamatari, Kisarazu City, Chiba Prefecture 292-0818, Japan) on May 19, 2020. Entrustment Number NITE B It is deposited internationally as P-03221. (a) Cell morphology Shape: Rod-shaped bacterium, Spore formation: (-), Motility: (-) (b) Colony morphology (The morphology of colonies cultured aerobically on MRS agar medium at 37°C for 24 hours was observed.) (1) Gram staining: (+) (2) Gas production: (-) (3) Catalase activity: (-) (4) Indole origin: (-) (5) Attitude towards oxygen: facultative anaerobic (6) Optimum growth temperature: 37~40℃ (7) Optimal growth pH: pH5.5~5.8 2) Strain #71, like strains #35 and #58, is a Lactobacillus salivarius strain possessing a 16S rRNA gene consisting of the nucleotide sequence of Sequence ID No. 1, and has the same characteristics as strains #35 and #58. Specifically, strain #71 has the following characteristics. Strain #71 was internationally deposited with the National Institute of Technology and Evaluation (NITE) Patent Microorganism Depositary Center (NPMD) (Address: Room 122, 2-5-8 Kazusa Kamatari, Kisarazu City, Chiba Prefecture 292-0818, Japan) on May 19, 2020. Entrustment Number NITE B It is deposited internationally as P-03220. (a) Cell morphology Shape: Rod-shaped bacterium, Spore formation: (-), Motility: (-) (b) Colony morphology (The morphology of colonies cultured aerobically on MRS agar medium at 37°C for 24 hours was observed.) (1) Gram staining: (+) (2) Gas production: (-) (3) Catalase activity: (-) (4) Indole origin: (-) (5) Attitude towards oxygen: facultative anaerobic (6) Optimum growth temperature: 37~40℃ (7) Optimal growth pH: pH5.5~5.8 【0092】 Example 12.2 Evaluation of the immunomodulatory capacity of strain #131 in this study against a straight-stranded RNA model virus. Regarding strain #131, similar to strains #35 and #58, in order to confirm that it enhances the antiviral immune response, PIE cell lines were stimulated with strain #131 before stimulating them with Poly I:C, and the expression of antiviral factors was analyzed. 【0093】 12-1 Method The analysis of the cellular immune response was performed according to the following procedures [1] to [4]. [1] Place the PIE cell line in a 12-well plate coated with type I collagen (Sumitomo Bakelite Co., Ltd.) in a 3 × 10⁶ 4 Seeds were seeded to achieve a cell / well density and cultured in DMEM liquid medium for 3 days. [2] The subject stock #131 was divided into 5.0 × 10 units per well. 7 The cells were added to the culture medium to a concentration of cells / mL and cultured (stimulated) for 48 hours. As a control of the unstimulated #131 cell line, the PIE cell line was cultured similarly in DMEM liquid medium without the #131 cell line. [3] After removing the culture medium and washing the cells twice with PBS, the medium was replaced with DMEM liquid medium containing 50 ng / mL of Poly I:C (catalog number P9582, SIGMA), and the cells were cultured for 12 hours to stimulate them with Poly I:C. As a control without Poly I:C stimulation, PIE cell lines were cultured in the same manner in DMEM liquid medium without Poly I:C. [4] After removing the culture medium, the procedure from the recovery of total RNA in the cells to the analysis of the expression level of the mRNA of the antiviral factor (IFN-β) gene was carried out according to steps [3] to [5] in the section [Analysis of cytokine-related factor expression in PIE cell lines stimulated with Poly I:C] of Example 1 above. The IFN-β expression level of the #131 cell line stimulated (see Figure 16) was calculated based on the formula ([expression level of mRNA of the IFN-β gene / expression level of mRNA of the β-actin gene] when the #131 cell line was stimulated before stimulation with Poly I:C / [expression level of mRNA of the IFN-β gene / expression level of mRNA of the β-actin gene] when stimulated with Poly I:C). In addition, as a control, the expression levels of various antiviral factors were also calculated when both the #131 cell line and Poly I:C were unstimulated (see Figure 16). 【0094】 4-2 Results Prior to stimulation with Poly I:C, the expression level of IFN-β in PIE cell lines stimulated with the #131 strain was significantly increased compared to the expression level in PIE cell lines that were not stimulated with the #131 strain but were stimulated with Poly I:C (see Figure 16). 【0095】 These results indicate that strain #131, like strains #35 and #58, possesses an effect of enhancing the expression of antiviral factors. Furthermore, since strains #35 and #58, as well as strains #131 and #71, are all Lactobacillus salivarius strains possessing a 16S rRNA gene consisting of the nucleotide sequence of SEQ ID NO: 1, it is suggested that Lactobacillus salivarius strains possessing a 16S rRNA gene consisting of the nucleotide sequence of SEQ ID NO: 1 possess both antiviral and wakame seaweed assimilation properties. 【0096】 Example 13. Confirmation of the viral infection reduction effect of the Lactobacillus bacterial strain in question (2) We analyzed whether bacterial strains of the Lactobacillus genus, even those of a different species from Lactobacillus salivarius, possessing high sequence identity with the nucleotide sequence of the 16S rRNA gene of Lactobacillus salivarius that exhibited antiviral effects (i.e., the nucleotide sequence of SEQ ID NO: 1). Specifically, we analyzed whether the Lactobacillus bacterial strains included in this study... 8 Types of Lactobacillus plantarum strains (strain #16, strain #6VG132, strain #6ML6109, strain #6ML686, strain #3CS123, strain #6VG141, strain #2CS82, and Case #1FeB18 (Co., Ltd.) and one type of Lactobacillus mucosae strain (this item #4FeB195 strain) A rotavirus infection test was conducted on this matter. 【0097】 This strain #16 is a Lactobacillus plantarum strain possessing a 16S rRNA gene consisting of the nucleotide sequence of Sequence ID No. 52, and was internationally deposited with the National Institute of Technology and Evaluation (NITE) Patent Microorganism Depository Center (NPMD) (Address: Room 122, 2-5-8 Kazusa-Kamatari, Kisarazu City, Chiba Prefecture 292-0818, Japan) on April 23, 2021. Entrustment Number NITE B It is internationally deposited as P-03474. This strain #16 has the following characteristics, similar to the four Lactobacillus salivarius strains mentioned above (strains #35, #58, #131, and #71). (a) Cell morphology Shape: Rod-shaped bacterium, Spore formation: (-), Motility: (-) (b) Colony morphology (The morphology of colonies cultured aerobically on MRS agar medium at 37°C for 24 hours was observed.) (1) Gram staining: (+) (2) Gas production: (-) (3) Catalase activity: (-) (4) Indole origin: (-) (5) Attitude towards oxygen: facultative anaerobic (6) Optimum growth temperature: 37~40℃ (7) Optimal growth pH: pH5.5~5.8 【0098】 1) The strain #6ML686 in question is a Lactobacillus plantarum strain possessing a 16S rRNA gene consisting of the nucleotide sequence of Sequence ID No. 53, and was internationally deposited with the National Institute of Technology and Evaluation (NITE) Patent Microorganism Depository Center (NPMD) (Address: Room 122, 2-5-8 Kazusa Kamatari, Kisarazu City, Chiba Prefecture 292-0818, Japan) on April 23, 2021. Entrustment Number NITE B It is internationally deposited as P-03466. This strain #6ML686 has the following characteristics, similar to the four Lactobacillus salivarius strains mentioned above (strains #35, #58, #131, and #71). (a) Cell morphology Shape: Rod-shaped bacterium, Spore formation: (-), Motility: (-) (b) Colony morphology (The morphology of colonies cultured aerobically on MRS agar medium at 37°C for 24 hours was observed.) (1) Gram staining: (+) (2) Gas production: (-) (3) Catalase activity: (-) (4) Indole origin: (-) (5) Attitude towards oxygen: facultative anaerobic (6) Optimum growth temperature: 37~40℃ (7) Optimal growth pH: pH5.5~5.8 2) The strain #6ML6109 is a Lactobacillus plantarum strain possessing a 16S rRNA gene consisting of the nucleotide sequence of Sequence ID No. 53, and was internationally deposited with the National Institute of Technology and Evaluation (NITE) Patent Microorganism Depository Center (NPMD) (Address: Room 122, 2-5-8 Kazusa Kamatari, Kisarazu City, Chiba Prefecture 292-0818, Japan) on April 23, 2021. Entrustment Number NITE B It is internationally deposited as P-03468. This strain #6ML6109 has the following characteristics, similar to the four Lactobacillus salivarius strains mentioned above (strains #35, #58, #131, and #71). (a) Cell morphology Shape: Rod-shaped bacterium, Spore formation: (-), Motility: (-) (b) Colony morphology (The morphology of colonies cultured aerobically on MRS agar medium at 37°C for 24 hours was observed.) (1) Gram staining: (+) (2) Gas production: (-) (3) Catalase activity: (-) (4) Indole origin: (-) (5) Attitude towards oxygen: facultative anaerobic (6) Optimum growth temperature: 37~40℃ (7) Optimal growth pH: pH5.5~5.8 【0099】 This strain, #6VG132, is a Lactobacillus plantarum strain possessing a 16S rRNA gene consisting of the nucleotide sequence of Sequence ID No. 54, and was internationally deposited with the National Institute of Technology and Evaluation (NITE) Patent Microorganism Depository Center (NPMD) (Address: Room 122, 2-5-8 Kazusa-Kamatari, Kisarazu City, Chiba Prefecture 292-0818, Japan) on April 23, 2021. Entrustment Number NITE B It is internationally deposited as P-03467. This strain #6VG132 has the following characteristics, similar to the four Lactobacillus salivarius strains mentioned above (strains #35, #58, #131, and #71). (a) Cell morphology Shape: Rod-shaped bacterium, Spore formation: (-), Motility: (-) (b) Colony morphology (The morphology of colonies cultured aerobically on MRS agar medium at 37°C for 24 hours was observed.) (1) Gram staining: (+) (2) Gas production: (-) (3) Catalase activity: (-) (4) Indole origin: (-) (5) Attitude towards oxygen: facultative anaerobic (6) Optimum growth temperature: 37~40℃ (7) Optimal growth pH: pH5.5~5.8 【0100】 This strain, #6VG141, is a Lactobacillus plantarum strain possessing a 16S rRNA gene consisting of the nucleotide sequence of Sequence ID No. 55, and was internationally deposited with the National Institute of Technology and Evaluation (NITE) Patent Microorganism Depository Center (NPMD) (Address: Room 122, 2-5-8 Kazusa-Kamatari, Kisarazu City, Chiba Prefecture 292-0818, Japan) on April 23, 2021. Entrustment Number NITE B It is internationally deposited as P-03469. This strain #6VG141 has the following characteristics, similar to the four Lactobacillus salivarius strains mentioned above (strains #35, #58, #131, and #71). (a) Cell morphology Shape: Rod-shaped bacterium, Spore formation: (-), Motility: (-) (b) Colony morphology (The morphology of colonies cultured aerobically on MRS agar medium at 37°C for 24 hours was observed.) (1) Gram staining: (+) (2) Gas production: (-) (3) Catalase activity: (-) (4) Indole origin: (-) (5) Attitude towards oxygen: facultative anaerobic (6) Optimum growth temperature: 37~40℃ (7) Optimal growth pH: pH5.5~5.8 【0101】 1) The #2CS82 strain is a Lactobacillus plantarum strain possessing a 16S rRNA gene consisting of the nucleotide sequence of Sequence ID No. 56, and was internationally deposited with the National Institute of Technology and Evaluation (NITE) Patent Microorganism Depository Center (NPMD) (Address: Room 122, 2-5-8 Kazusa Kamatari, Kisarazu City, Chiba Prefecture 292-0818, Japan) on April 23, 2021. Entrustment Number NITE B It is internationally deposited as P-03470. This strain #2CS82 has the following characteristics, similar to the four Lactobacillus salivarius strains mentioned above (strains #35, #58, #131, and #71). (a) Cell morphology Shape: Rod-shaped bacterium, Spore formation: (-), Motility: (-) (b) Colony morphology (The morphology of colonies cultured aerobically on MRS agar medium at 37°C for 24 hours was observed.) (1) Gram staining: (+) (2) Gas production: (-) (3) Catalase activity: (-) (4) Indole origin: (-) (5) Attitude towards oxygen: facultative anaerobic (6) Optimum growth temperature: 37~40℃ (7) Optimal growth pH: pH5.5~5.8 2) The #1FeB18 strain is a Lactobacillus plantarum strain possessing a 16S rRNA gene consisting of the nucleotide sequence of Sequence ID No. 56, and was internationally deposited with the National Institute of Technology and Evaluation (NITE) Patent Microorganism Depository Center (NPMD) (Address: Room 122, 2-5-8 Kazusa Kamatari, Kisarazu City, Chiba Prefecture 292-0818, Japan) on April 23, 2021. Entrustment Number NITE B It is internationally deposited as P-03472. This #1FeB18 strain has the following characteristics, similar to the four Lactobacillus salivarius strains mentioned above (this #35 strain, this #58 strain, this #131 strain, and this #71 strain). (a) Cell morphology Shape: Rod-shaped bacterium, Spore formation: (-), Motility: (-) (b) Colony morphology (The morphology of colonies cultured aerobically on MRS agar medium at 37°C for 24 hours was observed.) (1) Gram staining: (+) (2) Gas production: (-) (3) Catalase activity: (-) (4) Indole origin: (-) (5) Attitude towards oxygen: facultative anaerobic (6) Optimum growth temperature: 37~40℃ (7) Optimal growth pH: pH5.5~5.8 【0102】 This strain, #3CS123, is a Lactobacillus plantarum strain possessing a 16S rRNA gene consisting of the nucleotide sequence of Sequence ID No. 57, and was internationally deposited with the National Institute of Technology and Evaluation (NITE) Patent Microorganism Depository Center (NPMD) (Address: Room 122, 2-5-8 Kazusa-Kamatari, Kisarazu City, Chiba Prefecture 292-0818, Japan) on April 23, 2021. Entrustment Number NITE B It is internationally deposited as P-03471. This strain #3CS123 has the following characteristics, similar to the four Lactobacillus salivarius strains mentioned above (strains #35, #58, #131, and #71). (a) Cell morphology Shape: Rod-shaped bacterium, Spore formation: (-), Motility: (-) (b) Colony morphology (The morphology of colonies cultured aerobically on MRS agar medium at 37°C for 24 hours was observed.) (1) Gram staining: (+) (2) Gas production: (-) (3) Catalase activity: (-) (4) Indole origin: (-) (5) Attitude towards oxygen: facultative anaerobic (6) Optimum growth temperature: 37~40℃ (7) Optimal growth pH: pH5.5~5.8 【0103】 Furthermore, this strain #4FeB195 possesses a Lactobacillus gene consisting of the nucleotide sequence of SEQ ID NO: 58. Mucosae It is a stock and was internationally deposited with the Patent Microorganism Depositary Center (NPMD) of the National Institute of Technology and Evaluation (NITE) (Address: Room 122, 2-5-8 Kazusa Kamatari, Kisarazu City, Chiba Prefecture 292-0818, Japan) on April 23, 2021. Entrustment Number NITE B It is internationally deposited as P-03473. This strain #4FeB195 has the same characteristics as the four Lactobacillus salivarius strains mentioned above (strains #35, #58, #131, and #71). (a) Cell morphology Shape: Rod-shaped bacterium, Spore formation: (-), Motility: (-) (b) Colony morphology (The morphology of colonies cultured aerobically on MRS agar medium at 37°C for 24 hours was observed.) (1) Gram staining: (+) (2) Gas production: (-) (3) Catalase activity: (-) (4) Indole origin: (-) (5) Attitude towards oxygen: facultative anaerobic (6) Optimum growth temperature: 37~40℃ (7) Optimal growth pH: pH5.5~5.8 【0104】 the above 8 A variety of Lactobacillus plantarum strains and one strain of Lactobacillus mucosae These are all Lactobacillus bacterial strains that possess a 16S rRNA gene that is at least 90% identical to the nucleotide sequence of Sequence ID No. 1. 【0105】 13-1 Materials and Methods 【0106】 [material] The PIE1-3 cell line was created using cells cloned from the small intestine of weaned Duroc piglets. 【0107】 [method] Rotavirus infection testing and subsequent analysis of rotavirus infection levels and rotavirus-infected cells were performed according to the following procedures [1] to [7]. [1] Place the PIE1-3 cell line in a 96-well plate coated with type I collagen (Sumitomo Bakelite Co., Ltd.) in a 3 × 10⁶ well. 4 Seeds were seeded to a concentration of cells / mL and cultured in DMEM liquid medium for 8 days. [2] The above 8 A variety of Lactobacillus plantarum strains and one strain of Lactobacillus mucosae Each of these cells was added to the culture medium to a MOI of 1 per well, and cultured (stimulated) for 48 hours. As a control of these unstimulated cell lines, the PIE1-3 cell lines were cultured similarly in DMEM liquid medium without these cell lines. [3] The cells were washed three times with FCS-free DMEM liquid medium, and 100 μL (equivalent to 1 MOI) of the activated rotavirus solution prepared according to the method described in item [Preparation of activated rotavirus solution] of Example 6 was added to each well. The cells were incubated for 12 hours under 5% CO2 / 20% O2 and 37°C conditions. [4] After removing the activated rotavirus solution, 1 A strain of Lactobacillus plantarum (this case #1FeB18) (Co., Ltd.) and one type of Lactobacillus mucosae strain (this item #4FeB195 strain) For the PIE1-3 cell lines stimulated with , in order to analyze the proportion of rotavirus-infected cells, the procedure from cell fixation to indirect immunofluorescence was performed according to steps [4] to [7] in the section [Rotavirus infection test and indirect immunofluorescence method] of Example 6 above (see Figure 18). [5] Furthermore, for PIE1-3 cell lines stimulated with seven types of Lactobacillus plantarum strains (strain #16, strain #6VG132, strain #6ML6109, strain #6ML686, strain #3CS123, strain #6VG141, and strain #2CS82), the level of rotavirus infection was analyzed using the expression level of rotavirus-derived genes as an indicator. First, after removing the activated rotavirus solution, the cells were washed once with PBS, and total RNA in the cells was obtained according to standard procedures using cell lysate (TRIzol reagent [Invitrogen]). The concentration and purity of the RNA were measured using a NanoDrop ND-1000 spectrophotometer (Thermo Fisher Scientific). [6] cDNA was synthesized from the obtained total RNA using the Prime Script RT reagent Kit with gDNA Eraser (Perfect Real Time) (Takara Corporation) according to the protocol provided with the product. [7] Using the synthesized cDNA as a template, quantitative PCR analysis was performed to analyze the mRNA expression levels of the rotavirus-derived gene (NSP5 gene) and the β-actin gene using the primer set (sense primers and antisense primers) shown in Table 2 below, Platinum SYBR Green qPCR Super Mix-UDG with ROX (Invitrogen), and the ABI PRISM 7300 real-time PCR system (Applied Biosystems), according to the protocol provided with the product. 8 A variety of Lactobacillus plantarum strains and one strain of Lactobacillus mucosae The expression level of NSP5 in response to stimulation is given by the formula (above). 8 A variety of Lactobacillus plantarum strains and one strain of Lactobacillus mucosae Stimulation-induced [NSP5 gene mRNA expression level / β-actin gene mRNA expression level] / above 8 A variety of Lactobacillus plantarum strains and one strain of Lactobacillus mucosae The expression level was calculated based on the [expression level of NSP5 gene mRNA / expression level of β-actin gene mRNA] in the unstimulated state (see Figure 17). 【0108】 [Table 2] 【0109】 13-2 Results When PIE1-3 cell lines were stimulated with seven Lactobacillus plantarum strains (#16, #6VG132, #6ML6109, #6ML686, #3CS123, #6VG141, and #2CS82) before incubation with activated rotavirus solution, the expression level of rotavirus-derived NSP5 was significantly reduced compared to the unstimulated cells (see Figure 17). 【0110】 Also, before incubating the PIE1-3 cell line with activated rotavirus solution, 1 A strain of Lactobacillus plantarum (this case #1FeB18) (Co., Ltd.) and one type of Lactobacillus mucosae (strain #4FeB195)When stimulated, the proportion of rotavirus-infected cells in each strain was significantly reduced compared to the unstimulated strain (see Figure 18). 【0111】 These results are as described above. 8 Types of Lactobacillus plantarum strains and One strain of Lactobacillus mucosae This indicates that it has an effect of reducing (preventing) viral infection. [Industrial applicability] 【0112】 This invention contributes to the prevention or treatment of viral infections in livestock farming and human medicine.

Claims

[Claim 1] Lactobacillus salivarius strain deposited under accession number NITE BP-03218; Lactobacillus salivarius strain deposited under accession number NITE BP-03219; Lactobacillus salivarius strain deposited under accession number NITE BP-03221; Lactobacillus plantarum strain deposited under accession number NITE BP-03474; Lactobacillus plantarum strain deposited under accession number NITE BP-03467; Lactobacillus plantarum strain deposited under accession number NITE BP-03468; Lactobacillus plantarum strain deposited under accession number NITE BP-03466; Lactobacillus plantarum strain deposited under accession number NITE BP-03471; Lactobacillus plantarum strain deposited under accession number NITE BP-03469; Lactobacillus plantarum strain deposited under accession number NITE BP-03470; Lactobacillus plantarum strain deposited under accession number NITE BP-03472; and Lactobacillus mucosae strain deposited under accession number NITE BP-03473; An antiviral agent characterized by containing one or more Lactobacillus bacterial strains selected from the group consisting of the following. [Claim 2] The antiviral agent according to claim 1, characterized in that the virus is a double-stranded RNA virus. [Claim 3] The antiviral agent according to claim 1 or 2, characterized in that it is livestock feed or food / beverage. [Claim 4] Lactobacillus salivarius strain deposited under accession number NITE BP-03218; Lactobacillus salivarius strain deposited under accession number NITE BP-03219; Lactobacillus salivarius strain deposited under accession number NITE BP-03221; Lactobacillus plantarum strain deposited under accession number NITE BP-03474; Lactobacillus plantarum strain deposited under accession number NITE BP-03467; Lactobacillus plantarum strain deposited under accession number NITE BP-03468; Lactobacillus plantarum strain deposited under accession number NITE BP-03466; Accession number NITE Lactobacillus plantarum strain deposited as BP-03471; Lactobacillus plantarum strain deposited as accession number NITE BP-03469; Lactobacillus plantarum strain deposited as accession number NITE BP-03470; Lactobacillus plantarum strain deposited as accession number NITE BP-03472; or Lactobacillus mucosae strain deposited as accession number NITE BP-03473.

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