title: Contribution of NS1 effector domain dimerization to influenza A virus replication and virulence.
abstract: Conserved tryptophan-187 facilitates homodimerization of the influenza A virus NS1 protein effector domain. We generated a mutant influenza virus strain expressing NS1-W187R to destabilize this self-interaction. NS1-W187R protein exhibited lower double-stranded RNA (dsRNA)-binding activity, showed a temporal redistribution during infection, and was minimally compromised for interferon antagonism. The mutant virus replicated similarly to the wild type in vitro, but it was slightly attenuated for replication in mice, causing notably reduced morbidity and mortality. These data suggest biological relevance for the W187-mediated homotypic interaction of NS1.
authors.affiliation: Department of Microbiology, Mount Sinai School of Medicine, New York, New York, USA.
authors.forename: Juan
authors.initials: J
authors.lastname: Ayllon
authors.forename: Rupert J
authors.initials: RJ
authors.lastname: Russell
authors.forename: Adolfo
authors.initials: A
authors.lastname: García-Sastre
authors.forename: Benjamin G
authors.initials: BG
authors.lastname: Hale
mesh_terms: D000818:Animals; D015153:Blotting, Western; D019281:Dimerization; D004285:Dogs; D019084:Fluorescent Antibody Technique, Indirect; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics* / Q000472:pathogenicity* / Q000502:physiology; D008156:Luciferases; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D020125:Mutation, Missense / Q000235:genetics; D017361:Viral Nonstructural Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000502:physiology*
chemical_list: C085820:INS1 protein, influenza virus; D017361:Viral Nonstructural Proteins; D008156:Luciferases