The multifunctional NS1 protein of influenza A viruses.

By B. G. Hale, R. Randall, J. Ortín, D. Jackson. Journal of General Virology, 2008

1,117 citations recorded by the source corpus.

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.

Subfields: Epidemiology, Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/ba4755fc64674027de707bd023fbbfa26646cdef

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Citations in the corpus

• IFITM Proteins Mediate the Innate Immune Response to Influenza A H1N1 Virus, West Nile Virus and Dengue Virus (2009, background): “However, many viruses deploy anti-IFN countermeasures, which for influenza A virus are primarily enacted by the viral protein NS1 (Hale et al., 2008).”
• IFITM3 restricts the morbidity and mortality associated with influenza (2012, positive): “NS1 is the primary influenza virus interferon antagonist, with multiple inhibitory effects on host immune pathways 20, 21 .”
• A physical and regulatory map of host-influenza interactions reveals pathways in H1N1 infection. (2009, background): “These included the previously reported association between NS1 and STAU1, interactions between NS1 and PRKRA and TARBP2 (regulators of PKR-mediated transcription; for a review of NS1host interactions, see Hale et al. [2008]), and interactions between influenza and eight proteins that are targeted by”
• Influenza A virus NS1 targets the ubiquitin ligase TRIM25 to evade recognition by RIG-I (2009, background): “Several functions have been documented that may account for NS1 inhibition of type I IFN production, including sequestration of dsRNA, interaction with RIG-I, and inhibition of downstream processes after RIG-I-MAVS interactions such as the processing and trafficking of cellular mRNAs and the activit”
• Influenza Virus Evolution, Host Adaptation and Pandemic Formation (2010, background): “The non-structural 1 (NS1) protein has multiple functional domains, including N-terminal dsRNA binding (1–73) containing a nuclear localization signal (NLS), a central effector domain (73–207) containing a nuclear export signal and C-terminal region (207–230) containing a PDZ domain (Hale et al., 20”
• Influenza A viruses: new research developments (2011, background): “Another virulence determinant of influenza virus is the multifunctional protein NS1 (reviewed in Ref”