| RRC ID |
56591
|
| 著者 |
Watanabe Y, Arai Y, Kawashita N, Ibrahim MS, Elgendy EM, Daidoji T, Kajikawa J, Hiramatsu H, Sriwilaijaroen N, Ono T, Takagi T, Takahashi K, Shioda T, Matsumoto K, Suzuki Y, Nakaya T.
|
| タイトル |
Characterization of H5N1 Influenza Virus Quasispecies with Adaptive Hemagglutinin Mutations from Single-Virus Infections of Human Airway Cells.
|
| ジャーナル |
J Virol
|
| Abstract |
Transmission of avian influenza (AI) viruses to mammals involves phylogenetic bottlenecks that select small numbers of variants for transmission to new host species. However, little is known about the AI virus quasispecies diversity that produces variants for virus adaptation to humans. Here, we analyzed the hemagglutinin (HA) genetic diversity produced during AI H5N1 single-virus infection of primary human airway cells and characterized the phenotypes of these variants. During single-virus infection, HA variants emerged with increased fitness to infect human cells. These variants generally had decreased HA thermostability, an indicator of decreased transmissibility, that appeared to compensate for their increase in α2,6-linked sialic acid (α2,6 Sia) binding specificity and/or in the membrane fusion pH threshold, each of which is an advantageous mutational change for viral infection of human airway epithelia. An HA variant with increased HA thermostability also emerged but could not outcompete variants with less HA thermostability. These results provided data on HA quasispecies diversity in human airway cells.IMPORTANCE The diversity of the influenza virus quasispecies that emerges from a single infection is the starting point for viral adaptation to new hosts. A few studies have investigated AI virus quasispecies diversity during human adaptation using clinical samples. However, those studies could be appreciably affected by individual variability and multifactorial respiratory factors, which complicate identification of quasispecies diversity produced by selective pressure for increased adaptation to infect human airway cells. Here, we found that detectable HA genetic diversity was produced by H5N1 single-virus infection of human airway cells. Most of the HA variants had increased fitness to infect human airway cells but incurred a fitness cost of less HA stability. To our knowledge, this is the first report to characterize the adaptive changes of AI virus quasispecies produced by infection of human airway cells. These results provide a better perspective on AI virus adaptation to infect humans.
|
| 巻・号 |
92(11)
|
| 公開日 |
2018-6-1
|
| DOI |
10.1128/JVI.02004-17
|
| PII |
JVI.02004-17
|
| PMID |
29563293
|
| PMC |
PMC5952156
|
| MeSH |
Animals
Cell Line
Chlorocebus aethiops
Dogs
Genetic Variation / genetics
HEK293 Cells
Hemagglutinin Glycoproteins, Influenza Virus / genetics*
Humans
Influenza A Virus, H5N1 Subtype / classification
Influenza A Virus, H5N1 Subtype / genetics*
Influenza A Virus, H5N1 Subtype / pathogenicity*
Influenza, Human / pathology
Influenza, Human / transmission*
Influenza, Human / virology
Madin Darby Canine Kidney Cells
Quasispecies / genetics*
Receptors, Virus / genetics
Receptors, Virus / metabolism*
Respiratory Mucosa / cytology*
Respiratory Mucosa / virology
Respiratory System / virology
Sialic Acids / metabolism
Vero Cells
Virus Attachment
|
| IF |
4.324
|
| 引用数 |
5
|
| リソース情報 |
| ヒト・動物細胞 |
293T(RCB2202)
Vero(RCB0001)
MDCK(RCB0995) |
