A combination of HA and PA mutations enhances virulence in a mouse-adapted H6N6 influenza A virus.

ABSTRACT:

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H6N6 viruses are commonly isolated from domestic ducks, and avian-to-swine transmissions of H6N6 viruses have been detected in China. Whether subsequent adaptation of H6N6 viruses in mammals would increase their pathogenicity toward humans is not known. To address this, we generated a mouse-adapted (MA) swine influenza H6N6 virus (A/swine/Guangdong/K6/2010 [GDK6-MA]) which exhibited greater virulence than the wild-type virus (GDK6). Amino acid substitutions in PB2 (E627K), PA (I38M), and hemagglutinin ([HA] L111F, H156N, and S263R) occurred in GDK6-MA. HA with the H156N mutation [HA(H156N)] resulted in enlarged plaque sizes on MDCK cells and enhanced early-stage viral replication in mammalian cells. PA(I38M) raised polymerase activity in vitro but did not change virus re

SUBMITTER: Tan L 

PROVIDER: S-EPMC4249163 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature