A PB1-K577E mutation in H9N2 influenza virus increases polymerase activity and pathogenicity in mice
Haruhiko Kamiki, Hiromichi Matsugo, Tomoya Kobayashi, Hiroho Ishida, Akiko Takenaka-Uema, Shin Murakami, Taisuke Horimoto
H9N2 avian influenza viruses are present in poultry worldwide. These viruses are considered to have pandemic potential, because recent isolates can recognize human-type receptor and several sporadic human infections have been reported. In this study, we aimed to identify mutations related to mammalian adaptation of H9N2 influenza virus. We found that mouse-adapted viruses had several mutations in hemagglutinin (HA), PB2, PA, and PB1. Among the detected mutations, PB1-K577E was a novel mutation that had not been previously reported to involve mammalian adaptation. A recombinant H9N2 virus bearing only the PB1-K577E mutation showed enhanced pathogenicity in mice, with increased virus titers in nasal turbinates compared to that in mice infected with the wild-type virus. In addition, the PB1-K577E mutation increased virus polymerase activity in human cell culture at a lower temperature. These data suggest that the PB1-K577E mutation is a novel pathogenicity determinant of H9N2 virus in mice and could be a signature for mammalian adaptation.
- : Journal of Biological Chemistry
- : 10.3390/v10110653
- : http://www.mdpi.com/1999-4915/10/11/653/htm