| RRC ID |
57856
|
| 著者 |
Arai Y, Kawashita N, Ibrahim MS, Elgendy EM, Daidoji T, Ono T, Takagi T, Nakaya T, Matsumoto K, Watanabe Y.
|
| タイトル |
PB2 mutations arising during H9N2 influenza evolution in the Middle East confer enhanced replication and growth in mammals.
|
| ジャーナル |
PLoS Pathog
|
| Abstract |
Avian influenza virus H9N2 has been endemic in birds in the Middle East, in particular in Egypt with multiple cases of human infections since 1998. Despite concerns about the pandemic threat posed by H9N2, little is known about the biological properties of H9N2 in this epicentre of infection. Here, we investigated the evolutionary dynamics of H9N2 in the Middle East and identified phylogeny-associated PB2 mutations that acted cooperatively to increase H9N2 replication/transcription in human cells. The accumulation of PB2 mutations also correlated with an increase in H9N2 virus growth in the upper and lower airways of mice and in virulence. These mutations clustered on a solvent-exposed region in the PB2-627 domain in proximity to potential interfaces with host factors. These PB2 mutations have been found at high prevalence during evolution of H9N2 in the field, indicating that they have provided a selective advantage for viral adaptation to infect poultry. Therefore, continuous prevalence of H9N2 virus in the Middle East has generated a far more fit or optimized replication phenotype, leading to an expanded viral host range, including to mammals, which may pose public health risks beyond the current outbreaks.
|
| 巻・号 |
15(7)
|
| ページ |
e1007919
|
| 公開日 |
2019-7-1
|
| DOI |
10.1371/journal.ppat.1007919
|
| PII |
PPATHOGENS-D-19-00484
|
| PMID |
31265471
|
| PMC |
PMC6629154
|
| MeSH |
Animals
Evolution, Molecular
Female
HEK293 Cells
Host Specificity / genetics
Humans
Influenza A Virus, H9N2 Subtype / genetics*
Influenza A Virus, H9N2 Subtype / pathogenicity*
Influenza A Virus, H9N2 Subtype / physiology
Influenza, Human / epidemiology
Influenza, Human / virology*
Mammals / virology
Mice
Mice, Inbred BALB C
Middle East / epidemiology
Models, Molecular
Mutation*
Orthomyxoviridae Infections / virology
Phylogeny
RNA-Dependent RNA Polymerase / chemistry
RNA-Dependent RNA Polymerase / genetics*
RNA-Dependent RNA Polymerase / metabolism
Reassortant Viruses / genetics
Reassortant Viruses / pathogenicity
Reassortant Viruses / physiology
Viral Proteins / chemistry
Viral Proteins / genetics*
Viral Proteins / metabolism
Virulence / genetics
Virus Replication / genetics
Zoonoses / virology
|
| IF |
6.218
|
| 引用数 |
4
|
| リソース情報 |
| ヒト・動物細胞 |
MDCK(RCB0995)
293T(RCB2202) |
