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Pneumovirus NS proteins antagonising interferon (IFN) response

An interferon and anti-virus technology, applied in the direction of anti-viral agents, antisense single-stranded RNA viruses, viruses, etc., can solve problems such as the unknown function of NS protein

Inactive Publication Date: 2009-04-01
WYETH LLC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, until now, the function of the NS protein is still unknown

Method used

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  • Pneumovirus NS proteins antagonising interferon (IFN) response
  • Pneumovirus NS proteins antagonising interferon (IFN) response
  • Pneumovirus NS proteins antagonising interferon (IFN) response

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Experimental program
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Embodiment Construction

[0017] To study the function of RSV proteins in more detail, deletion mutants of BRSV lacking the NS1 gene or both NS1 and NS2 genes were generated and their expression was studied in different cell lines.

[0018] The first phenomenon was observed after infection of MDBK cells (very sensitive to wt BRSV infection, and the titer of wt BRSV was higher than all other cell lines tested), that is, the sensitivity of NS deletion mutants to host cytokines was reduced. improved. However, viruses lacking one or both NS genes grew poorly in MDBK cells, whereas in other cell lines such as Vero or BSR, the lack of NS genes only reduced infection titers by a factor of 10. Co-culture experiments confirmed that type I interferon, a decisive host cytokine, was produced by BRSV-infected MDBK cells. Apparently, in infected MDBK cultures, an antiviral state can be induced by stimulation of autocrine and paracrine cells. Although wt BRSV was able to counteract this response, none of the NS del...

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Abstract

The present invention relates to the use of a pneumovirus NS1 protein and / or NS2 protein or a nucleic acid encoding pneumovirus NS1 protein and / or NS2 protein for the preparation of a pharmaceutical formulation for reducing the immune response mediated by interferon (IFN). The invention further relates to recombinant pneumoviruses, in particular respiratory syncytial viruses (RSV), having an increased, reduced, or lacking a resistance to the interferon (IFN) mediated immune response, recombinant viruses having an increased resistance to the interferon (IFN) mediated immune response, and the use of the viruses in pharmaceutical applications, e.g. as vaccines.

Description

Background of the invention [0001] Technical Field of the Invention [0002] The present invention relates to the use of pneumovirus NS1 protein and / or NS2 protein or nucleic acid encoding pneumovirus NS1 protein and / or NS2 protein to produce a pharmaceutical preparation for weakening interferon (IFN)-mediated immune response. The invention further relates to recombinant pneumoviruses, in particular respiratory syncytial virus (RSV) with enhanced, attenuated or lacking resistance to host interferon (IFN) mediated immune responses to interferon (IFN) mediated immune responses Recombinant viruses with increased resistance, and the use of these viruses in pharmaceutical formulations (eg, vaccines). [0003] Description of prior art [0004] Bovine respiratory syncytial virus (BRSV) is the most important causative agent of respiratory disease in calves, causing significant economic losses (40; 45). The immune response and pathology that occurred in calves in 2010 resembled the ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12N7/01A61K38/00A61P37/02C07K14/135A61K38/16C12N15/09A61K35/74A61K35/76A61K39/00A61K39/12A61K48/00A61P11/00A61P31/12A61P31/14A61P35/00A61P37/06A61P43/00C12N7/00C12N15/33
CPCA61K38/162A61K2039/525A61K2039/53A61K48/00C07K14/005C12N2760/18522A61P11/00A61P31/12A61P31/14A61P31/16A61P35/00A61P37/02A61P37/06A61P43/00C12N15/11
Inventor K·-K·孔泽尔曼
Owner WYETH LLC
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