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The multifunctional NS1 protein of influenza A viruses

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Hale2008JnlGenVirology89MultifunctionalNS1.pdf (534.8Kb)
Date
10/2008
Author
Hale, Benjamin Geoffrey
Randall, Richard Edward
Ortin, J
Jackson, David
Keywords
Double-stranded-rna
Viral messenger-rna
Temperature-sensitive mutants
Translation initiation-factor
Infected-cells
In-vivo
Nucleoctyoplasmic transport
Antiviral responses
Epithelial-cells
Mammalian-cells
QR355 Virology
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Abstract
The non-structural (NS1) protein of influenza A viruses is a non-essential virulence factor that has multiple accessory functions during viral infection. In recent years, the major role ascribed to NS1 has been its inhibition of host immune responses, especially the limitation of both interferon (IFN) production and the antiviral effects of IFN-induced proteins, such as dsRNA-dependent protein kinase R (PKR) and 2'5'-oligoadenylate synthetase (OAS)/RNase L. However, it is clear that NS1 also acts directly to modulate other important aspects of the virus replication cycle, including viral RNA replication, viral protein synthesis, and general host-cell physiology. Here, we review the current literature on this remarkably multifunctional viral protein. In the first part of this article, we summarize the basic biochemistry of NS1, in particular its synthesis, structure, and intracellular localization. We then discuss the various roles NS1 has in regulating viral replication mechanisms, host innate/adaptive immune responses, and cellular signalling pathways. We focus on the NS1-RNA and NS1-protein interactions that are fundamental to these processes, and highlight apparent strain-specific ways in which different NS1 proteins may act. In this regard, the contributions of certain NS1 functions to the pathogenicity of human and animal influenza A viruses are also discussed. Finally, we outline practical applications that future studies on NS1 may lead to, including the rational design and manufacture of influenza vaccines, the development of novel antiviral drugs, and the use of oncolytic influenza A viruses as potential anti-cancer agents.
Citation
Hale , B G , Randall , R E , Ortin , J & Jackson , D 2008 , ' The multifunctional NS1 protein of influenza A viruses ' , Journal of General Virology , vol. 89 , no. 10 , pp. 2359-2376 . https://doi.org/10.1099/vir.0.2008/004606-0
Publication
Journal of General Virology
Status
Peer reviewed
DOI
https://doi.org/10.1099/vir.0.2008/004606-0
ISSN
0022-1317
Type
Journal article
Rights
(c) 2008 SGM. This is an open access article published in Journal of General Virology
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  • University of St Andrews Research
URL
http://www.scopus.com/inward/record.url?scp=54449099369&partnerID=8YFLogxK
URI
http://hdl.handle.net/10023/3001

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