tetano
Editor, Senior Moderator
Published ahead of print 19 September 2012, doi: 10.1128/JVI.02237-12
Contribution of NS1 effector domain dimerization to influenza A virus replication and virulence
Juan Ayllon1,
Rupert J. Russell4,
Adolfo Garc?a-Sastre1,2,3 and
Benjamin G. Hale1,?
1Department of Microbiology
2Department of Medicine
3Global Health and Emerging Pathogens Institute, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA
4Biomedical Sciences Research Complex, University of St. Andrews, North Haugh, St. Andrews, Fife KY16 9ST, UK
ABSTRACT
Conserved tryptophan-187 facilitates homodimerization of the influenza A virus NS1 effector domain. We generated a mutant influenza virus expressing NS1-W187R to destabilize this self-interaction. NS1-W187R protein exhibited lower dsRNA-binding activity, showed a temporal redistribution during infection, and was minimally compromised for interferon-antagonism. The mutant virus replicated similarly to wild-type in vitro, but was slightly attenuated for replication in mice, causing notably reduced morbidity/mortality. These data suggest biological relevance for the W187-mediated homotypic interaction of NS1.
http://jvi.asm.org/content/early/2012/09/13/JVI.02237-12.abstract
Contribution of NS1 effector domain dimerization to influenza A virus replication and virulence
Juan Ayllon1,
Rupert J. Russell4,
Adolfo Garc?a-Sastre1,2,3 and
Benjamin G. Hale1,?
1Department of Microbiology
2Department of Medicine
3Global Health and Emerging Pathogens Institute, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA
4Biomedical Sciences Research Complex, University of St. Andrews, North Haugh, St. Andrews, Fife KY16 9ST, UK
ABSTRACT
Conserved tryptophan-187 facilitates homodimerization of the influenza A virus NS1 effector domain. We generated a mutant influenza virus expressing NS1-W187R to destabilize this self-interaction. NS1-W187R protein exhibited lower dsRNA-binding activity, showed a temporal redistribution during infection, and was minimally compromised for interferon-antagonism. The mutant virus replicated similarly to wild-type in vitro, but was slightly attenuated for replication in mice, causing notably reduced morbidity/mortality. These data suggest biological relevance for the W187-mediated homotypic interaction of NS1.
http://jvi.asm.org/content/early/2012/09/13/JVI.02237-12.abstract