AYLLON J, Russell RJ, Garcia-Sastre A, Hale BG, et. Contribution of NS1 effector domain dimerization to influenza A virus replication and virulence. J Virol. 2012
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.
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