Next Article in Journal
HIV-Enhancing and HIV-Inhibiting Properties of Cationic Peptides and Proteins
Previous Article in Journal
Implementation of Objective PASC-Derived Taxon Demarcation Criteria for Official Classification of Filoviruses
Article Menu
Issue 5 (May) cover image

Export Article

Open AccessArticle
Viruses 2017, 9(5), 107; doi:10.3390/v9050107

A Conserved Residue, Tyrosine (Y) 84, in H5N1 Influenza A Virus NS1 Regulates IFN Signaling Responses to Enhance Viral Infection

1
Toronto General Hospital Research Institute, University Health Network, 67 College Street, Toronto, ON M5G 2M1, Canada
2
Department of Immunology, University of Toronto, 1 King’s College Circle, Toronto, ON M5S 1A8, Canada
3
Center for Molecular Design and Preformulations, University Health Network, 101 College Street, Toronto, ON M5G 1L7, Canada
4
Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street, Toronto, ON M5S 3M2, Canada
5
Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON K1H 8M5, Canada
*
Author to whom correspondence should be addressed.
Academic Editor: Andrew Mehle
Received: 9 May 2017 / Accepted: 10 May 2017 / Published: 12 May 2017
(This article belongs to the Section Animal Viruses)
View Full-Text   |   Download PDF [13914 KB, uploaded 12 May 2017]   |  

Abstract

The non-structural protein, NS1, is a virulence factor encoded by influenza A viruses (IAVs). In this report, we provide evidence that the conserved residue, tyrosine (Y) 84, in a conserved putative SH2-binding domain in A/Duck/Hubei/2004/L-1 [H5N1] NS1 is critical for limiting an interferon (IFN) response to infection. A phenylalanine (F) substitution of this Y84 residue abolishes NS1-mediated downregulation of IFN-inducible STAT phosphorylation, and surface IFNAR1 expression. Recombinant IAV (rIAV) [H1N1] expressing A/Grey Heron/Hong Kong/837/2004 [H5N1] NS1-Y84F (rWSN-GH-NS1-Y84F) replicates to lower titers in human lung epithelial cells and is more susceptible to the antiviral effects of IFN-β treatment compared with rIAV expressing the intact H5N1 NS1 (rWSN-GH-NS1-wt). Cells infected with rWSN-GH-NS1-Y84F express higher levels of IFN stimulated genes (ISGs) associated with an antiviral response compared with cells infected with rWSN-GH-NS1-wt. In mice, intranasal infection with rWSN-GH-NS1-Y84F resulted in a delay in onset of weight loss, reduced lung pathology, lower lung viral titers and higher ISG expression, compared with mice infected with rWSN-GH-NS1-wt. IFN-β treatment of mice infected with rWSN-GH-NS1-Y84F reduced lung viral titers and increased lung ISG expression, but did not alter viral titers and ISG expression in mice infected with rWSN-GH-NS1-wt. Viewed altogether, these data suggest that the virulence associated with this conserved Y84 residue in NS1 is, in part, due to its role in regulating the host IFN response. View Full-Text
Keywords: influenza A viruses; non-structural protein 1; interferon-β; interferon signaling; interferon-stimulated genes influenza A viruses; non-structural protein 1; interferon-β; interferon signaling; interferon-stimulated genes
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Wang, B.X.; Wei, L.; Kotra, L.P.; Brown, E.G.; Fish, E.N. A Conserved Residue, Tyrosine (Y) 84, in H5N1 Influenza A Virus NS1 Regulates IFN Signaling Responses to Enhance Viral Infection. Viruses 2017, 9, 107.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Viruses EISSN 1999-4915 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top