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Nitric oxide inhibits rhinovirus infection

A technology of rhinoviruses and compounds, applied in the field of human rhinoviruses and virology, can solve problems such as effects to be studied

Inactive Publication Date: 2000-12-20
THE JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, to date, nothing is known about the specific biochemical events associated with each of these rhinovirus-induced cytokines, and the role of specific cytokines and other cytokines that occur during colds remains to be studied

Method used

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  • Nitric oxide inhibits rhinovirus infection
  • Nitric oxide inhibits rhinovirus infection
  • Nitric oxide inhibits rhinovirus infection

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] Effect of cell passage: Preliminary studies have shown that repeated cell passage can have a significant effect on cytokine production in BEAS-2B cells. Although qualitatively the data obtained are always the same for each passage, cell passage has a progressive effect on the absolute levels of cytokines produced. For example, in 4 experiments using the same method of serial cell passage, the amount of IL-8 production decreased from 7690pg / ml to 3090pg / ml. Therefore, each experiment performed below was always performed in conjunction with an experiment using the same cell passage.

[0044] A comparison of the effects of several rhinovirus strains on cytokine production in BEAS-2B cells: The effects of four different rhinovirus strains at equal infectious doses on cytokine production were compared, using cell culture The object is BEAS-2B cells. Three of the virus strains used above are type 14, type 16 and type 19, which are members of the major group (major group) of...

Embodiment 2

[0053] Kinetics of cytokine mRNA expression and protein secretion: Figure 2 shows that the mRNA levels of IL-8 and IL-6 were significantly increased within 1 hour after HRV-14 infection. At 24 hours post-infection, maximum expression had been reached for 3 hours but mRNA levels were still higher than uninfected controls. As mRNA was induced, IL-8 and IL-6 proteins in the supernatant were significantly increased. Cytokine production increased at 3 hours post-infection, reaching a maximum concentration at 24 hours. Notably, the time course of IL-8 and IL-6 production was faster after HRV-16 infection than after HRV-14 infection (Fig. 3). mRNA expression levels were highest within 1 hour post-infection and protein production was greatest within 7 hours. Consistent with the data shown above (FIG. 1), the amount of cytokines produced after HRV-16 infection was approximately 4-fold greater than after HRV-14 infection (FIG. 3 compared to FIG. 2). Since HRV-16 induces cytokine prod...

Embodiment 3

[0055] Virus titer after HRV-16 infection: The supernatant was collected at different time points after infection, and WI-38 cells were used for cytotoxicity experiments to determine the virus titer of HRV-16. Viruses could be detected in the culture medium about 7 hours after infection, and gradually increased during the period from 7 to 24 hours after infection (Table 1). Supernatants were collected during the second 24 hour post-infection period where virus levels approximated those observed after 24 hours (see Table 2 below). Indeed, this viral titer pattern was consistent with what was previously observed with HRV-14 (49).

[0056] Table 1

[0057] Human rhinovirus-16 infection from BEAS-2B cell cultures at different times

[0058] Virus content in the obtained supernatant

[0059] Time after infection Virus titer

[0060] (hour) (LogTCID 50 unit)*

[0061] 0 ND

[0062] 1 ND

[0063] 3 N...

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Abstract

Nitric oxide generating compounds or compounds which induce in situ synthesis of nitric oxide can be used to inhibit rhinovirus infection. Nitric oxide has the ability to inhibit both viral replication as well as the synthesis of cytokines, in particular the proinflammatory cytokines. Thus the symptoms of rhinovirus infections can be ameliorated by treatments to increase nitric oxide in the respiratory tract.

Description

[0001] This application claims priority to Application Serial No. 60 / 052,307, filed July 11,1997. [0002] This invention was made with US government support under grant AI37163 from the National Institutes of Health. Accordingly, the government has certain rights in this invention. [0003] technical field of invention [0004] The present invention relates to the field of virology. More specifically, the invention relates to the field of human rhinoviruses. Background of the invention [0005] Rhinovirus infection is a major cause of the common cold (18), the most prevalent respiratory disease in humans. There is also recent evidence that rhinovirus infection plays an important role in the exacerbation of asthma (21, 22, 37), chronic bronchitis (35), sinusitis (19, 50) and otitis media (3). Despite the enormous medical costs associated with rhinovirus infection, little is known about the underlying pathogenesis of viral infection leading to clinical symptoms. [0006] E...

Claims

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Application Information

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IPC IPC(8): A61K9/00A61K31/00A61K31/15A61K31/198A61P31/16
CPCA61K31/00A61K31/15A61K31/198A61K9/0043A61K9/0073A61P31/12A61P31/16A61K31/13
Inventor S·P·桑德斯D·普洛德
Owner THE JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE
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