HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: vir.0.007518-0v1 90/5/1109    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Xing, Z. Articles by Woolcock, P. R. Search for Related Content PubMed PubMed Citation Articles by Xing, Z. Articles by Woolcock, P. R. Agricola Articles by Xing, Z. Articles by Woolcock, P. R.

Differential regulation of antiviral and proinflammatory cytokines and suppression of Fas-mediated apoptosis by NS1 of H9N2 avian influenza virus in chicken macrophages

¹ Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, CA 95616, USA
² Veterinary Medicine Extension, School of Veterinary Medicine, University of California, Davis, CA 95616, USA
³ Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA 95616, USA
⁴ College of Veterinary Medicine, Northwest A & F University, Yangling 712100, PR China
⁵ Department of Veterinary Medicine, University of Maryland at College Park and Virginia-Maryland Regional College of Veterinary Medicine, College Park, MD 20742, USA
⁶ California Animal Health and Food Safety Laboratory System-Fresno Branch, University of California, Davis, CA 95616, USA

Correspondence
Zheng Xing
zxing{at}ucdavis.edu

The NS1 protein is known to suppress immune responses in influenza virus-infected hosts. However, the role of NS1 in apoptosis in infected cells is disputed. In this study, through the use of a mutant A/pheasant/California/2373/1998 (H9N2) avian influenza virus (AIV) with a truncated NS1, we have demonstrated that a functional NS1 protein suppresses the induction of interferons in chicken macrophages. However, NS1 appeared to be irrelevant to the regulation of cytokines interleukin (IL)-1β and IL-6, indicating that distinct mechanisms may be employed in the regulation of antiviral and proinflammatory cytokines in chicken immune cells. Our study also showed that this H9N2 AIV induced apoptosis extrinsically through the Fas/Fas ligand (FasL)-mediated pathway. We found that NS1 suppressed the apoptotic process through suppression of the induction of FasL, but not tumour necrosis factor- or TNF-related apoptosis-inducing ligand. Furthermore, our data indicated that the disruption of a potential binding site for the p85β subunit of phosphoinositide 3-kinase in the carboxyl terminus of NS1, while having no effect on the regulation of IFN induction, may contribute to the suppression of Fas/FasL-mediated apoptosis. Therefore, suppression of Fas/FasL-mediated apoptosis by NS1 is one of the critical mechanisms necessary to increase infectivity in AIV-infected chicken macrophages.

This article has been cited by other articles:

				B. G. Hale, P. S. Kerry, D. Jackson, B. L. Precious, A. Gray, M. J. Killip, R. E. Randall, and R. J. Russell Structural insights into phosphoinositide 3-kinase activation by the influenza A virus NS1 protein PNAS, February 2, 2010; 107(5): 1954 - 1959. [Abstract] [Full Text] [PDF]

				Z. Xing, C. J. Cardona, J. Anunciacion, S. Adams, and N. Dao Roles of the ERK MAPK in the regulation of proinflammatory and apoptotic responses in chicken macrophages infected with H9N2 avian influenza virus J. Gen. Virol., February 1, 2010; 91(2): 343 - 351. [Abstract] [Full Text] [PDF]