PB2 and hemagglutinin mutations are major determinants of host range and virulence in mouse-adapted influenza A virus.

ABSTRACT: Serial mouse lung passage of a human influenza A virus, A/Hong Kong/1/68 (H3N2) (HK-wt), produced a mouse-adapted variant, MA, with nine mutations that was >10(3.8)-fold more virulent. In this study, we demonstrate that MA mutations of the PB2 (D701N) and hemagglutinin (HA) (G218W in HA1 and T156N in HA2) genes were the most adaptive genetic determinants for increased growth and virulence in the mouse model. Recombinant viruses expressing each of the mutated MA genome segments on the HK-wt backbone showed significantly increased disease severity, whereas only the mouse-adapted PB2 gene increased virulence, as determined by the 50% lethal dose ([LD(50)] >10(1.4)-fold). The converse comparisons of recombinant MA viruses expressing each of the HK-wt genome segments showed the greatest decreas

SUBMITTER: Ping J 

PROVIDER: S-EPMC2950562 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature