Genome-wide characterization of the seasonal H3N2 virus in Shanghai reveals natural temperature-sensitive strains conferred by the I668V mutation in the PA subunit
| Autor: | De-Ming Yu, Jie-Ming Qu, Dong Wei, Mingjie Wang, Dong-Hua Zhang, Qi-jian Cheng, Xin-xin Zhang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Adult Male China Epidemiology viruses Immunology Mutation Missense lcsh:QR1-502 Virulence Genome Viral Biology medicine.disease_cause Microbiology Virus Article lcsh:Microbiology lcsh:Infectious and parasitic diseases 03 medical and health sciences Viral Proteins Young Adult Phylogenetics Virology Drug Discovery Influenza Human Influenza A virus medicine Humans lcsh:RC109-216 Polymerase Phylogeny Aged Aged 80 and over Mutation Influenza A Virus H3N2 Subtype Temperature General Medicine Middle Aged RNA-Dependent RNA Polymerase 030104 developmental biology Infectious Diseases Viral replication Viral evolution biology.protein Parasitology Female Seasons |
| Zdroj: | Emerging Microbes and Infections, Vol 7, Iss 1, Pp 1-12 (2018) Emerging Microbes & Infections |
| ISSN: | 2222-1751 |
| DOI: | 10.1038/s41426-018-0172-4 |
| Popis: | Seasonal H3N2 influenza viruses are recognized as major epidemic viruses, exhibiting complex seasonal patterns in regions with temperate climates. To investigate the influence of viral evolution and mutations on the seasonality of influenza, we performed a genome-wide analysis of samples collected from 62 influenza A/H3N2-infected patients in Shanghai during 2016–2017. Phylogenetic analysis of all eight segments of the influenza A virus revealed that there were two epidemic influenza virus strains circulating in the 2016–2017 winter season (2016–2017win) and 2017 summer season (2017sum). Replication of the two epidemic viral strains at different temperatures (33, 35, 37, and 39 °C) was measured, and the correlation of the mutations in the two epidemic viral strains with temperature sensitivity and viral replication was analyzed. Analysis of the replication kinetics showed that replication of the 2016–2017win strains was significantly restricted at 39 °C compared with that of the 2017sum strains. A polymerase activity assay and mutational analysis demonstrated that the PA I668V mutation of the 2016–2017win viruses suppressed polymerase activity in vitro at high temperatures. Taken together, these data suggest that the I668V mutation in the PA subunit of the 2016–2017win strains may confer temperature sensitivity and attenuate viral replication and polymerase activity; meanwhile, the 2017sum strains maintained virulence at high temperatures. These findings highlight the importance of certain mutations in viral adaptation and persistence in subsequent seasons. |
| Databáze: | OpenAIRE |
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