| RRC ID |
68110
|
| 著者 |
Arai Y, Kawashita N, Daidoji T, Ibrahim MS, El-Gendy EM, Takagi T, Takahashi K, Suzuki Y, Ikuta K, Nakaya T, Shioda T, Watanabe Y.
|
| タイトル |
Novel Polymerase Gene Mutations for Human Adaptation in Clinical Isolates of Avian H5N1 Influenza Viruses.
|
| ジャーナル |
PLoS Pathog
|
| Abstract |
A major determinant in the change of the avian influenza virus host range to humans is the E627K substitution in the PB2 polymerase protein. However, the polymerase activity of avian influenza viruses with a single PB2-E627K mutation is still lower than that of seasonal human influenza viruses, implying that avian viruses require polymerase mutations in addition to PB2-627K for human adaptation. Here, we used a database search of H5N1 clade 2.2.1 virus sequences with the PB2-627K mutation to identify other polymerase adaptation mutations that have been selected in infected patients. Several of the mutations identified acted cooperatively with PB2-627K to increase viral growth in human airway epithelial cells and mouse lungs. These mutations were in multiple domains of the polymerase complex other than the PB2-627 domain, highlighting a complicated avian-to-human adaptation pathway of avian influenza viruses. Thus, H5N1 viruses could rapidly acquire multiple polymerase mutations that function cooperatively with PB2-627K in infected patients for optimal human adaptation.
|
| 巻・号 |
12(4)
|
| ページ |
e1005583
|
| 公開日 |
2016-4-1
|
| DOI |
10.1371/journal.ppat.1005583
|
| PII |
PPATHOGENS-D-15-02586
|
| PMID |
27097026
|
| PMC |
PMC4838241
|
| MeSH |
Adaptation, Physiological / genetics*
Animals
Blotting, Western
DNA-Directed RNA Polymerases / genetics*
Disease Models, Animal
Female
Humans
Influenza A Virus, H5N1 Subtype
Influenza, Human / genetics*
Mice
Mice, Inbred BALB C
Mutagenesis, Site-Directed
Mutation
Real-Time Polymerase Chain Reaction
Transfection
Viral Proteins / genetics*
|
| IF |
2.985
|
| リソース情報 |
| ヒト・動物細胞 |
293T(RCB2202)
MDCK(RCB0995) |
