RRC ID |
54744
|
Author |
Kamiki H, Matsugo H, Kobayashi T, Ishida H, Takenaka-Uema A, Murakami S, Horimoto T.
|
Title |
A PB1-K577E Mutation in H9N2 Influenza Virus Increases Polymerase Activity and Pathogenicity in Mice.
|
Journal |
Viruses
|
Abstract |
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.
|
Volume |
10(11)
|
Published |
2018-11-19
|
DOI |
10.3390/v10110653
|
PII |
v10110653
|
PMID |
30463209
|
PMC |
PMC6266086
|
MeSH |
Adaptation, Biological
Animals
Disease Models, Animal
HEK293 Cells
Humans
Influenza A Virus, H9N2 Subtype / enzymology*
Influenza A Virus, H9N2 Subtype / genetics
Influenza A Virus, H9N2 Subtype / pathogenicity*
Mice
Mutation, Missense*
Nasal Cavity / virology
Orthomyxoviridae Infections / pathology
Orthomyxoviridae Infections / virology*
Temperature
Viral Load
Viral Proteins / genetics*
Viral Proteins / metabolism*
Virus Replication / radiation effects
|
IF |
3.811
|
Times Cited |
11
|
Resource |
Human and Animal Cells |
293T(RCB2202) |