tetano
Editor, Senior Moderator
Viruses. 2018 Nov 19;10(11). pii: E653. doi: 10.3390/v10110653.
[h=1]A PB1-K577E Mutation in H9N2 Influenza Virus Increases Polymerase Activity and Pathogenicity in Mice.[/h] Kamiki H[SUP]1[/SUP], Matsugo H[SUP]2[/SUP], Kobayashi T[SUP]3[/SUP], Ishida H[SUP]4[/SUP], Takenaka-Uema A[SUP]5[/SUP], Murakami S[SUP]6[/SUP], Horimoto T[SUP]7[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
[h=4]KEYWORDS:[/h] H9N2; PB1; influenza; mouse adaptation; polymerase
PMID: 30463209 DOI: 10.3390/v10110653
[h=1]A PB1-K577E Mutation in H9N2 Influenza Virus Increases Polymerase Activity and Pathogenicity in Mice.[/h] Kamiki H[SUP]1[/SUP], Matsugo H[SUP]2[/SUP], Kobayashi T[SUP]3[/SUP], Ishida H[SUP]4[/SUP], Takenaka-Uema A[SUP]5[/SUP], Murakami S[SUP]6[/SUP], Horimoto T[SUP]7[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
[h=4]KEYWORDS:[/h] H9N2; PB1; influenza; mouse adaptation; polymerase
PMID: 30463209 DOI: 10.3390/v10110653