RT info:eu-repo/semantics/article T1 Contribution of NS1 Effector Domain Dimerization to Influenza A Virus Replication and Virulence A1 Ayllón Barasoain, Juan A1 Russell, Rupert J. A1 García Sastre, Adolfo A1 Hale, Benjamin G. K1 Medicina K1 Medicine K1 Salud K1 Health K1 Microbiología K1 Microbiology K1 Enfermedades infecciosas K1 Communicable diseases AB 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. PB American Society for Microbiology SN 0022-538X YR 2012 FD 2012-12 LK http://hdl.handle.net/10259/9528 UL http://hdl.handle.net/10259/9528 LA eng NO This work was supported by NIH funding to A.G.-S. (under grantsR01AI046954 and U19AI083025, and CRIP, Center for Research on In-fluenza Pathogenesis, an NIAID Center of Excellence for Influenza Re-search and Surveillance [CEIRS], contract HHSN266200700010C). Con-focal laser scanning microscopy was performed at the MSSM-MicroscopyShared Resource Facility, supported with funding from a National Insti-tutes of Health-National Cancer Institute (NIH-NCI) shared resourcesgrant (5R24 CA095823-04), an NSF Major Research Instrumentationgrant (DBI-9724504), and an NIH shared instrumentation grant (1 S10RR0 9145-01) DS Repositorio Institucional de la Universidad de Burgos RD 23-nov-2024