TY - JOUR
T1 - Differential regulation of antiviral and proinflammatory cytokines and suppression of Fas-mediated apoptosis by NS1 of H9N2 avian influenza virus in chicken macrophages
AU - Xing, Zheng
AU - Cardona, Carol J.
AU - Adams, Sean
AU - Yang, Zengqi
AU - Li, Jinling
AU - Perez, Daniel
AU - Woolcock, Peter R.
PY - 2009
Y1 - 2009
N2 - 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-α 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.
AB - 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-α 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.
UR - http://www.scopus.com/inward/record.url?scp=67449106151&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67449106151&partnerID=8YFLogxK
U2 - 10.1099/vir.0.007518-0
DO - 10.1099/vir.0.007518-0
M3 - Article
C2 - 19264628
AN - SCOPUS:67449106151
SN - 0022-1317
VL - 90
SP - 1109
EP - 1118
JO - Journal of General Virology
JF - Journal of General Virology
IS - 5
ER -