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Virol Sin
. 2023 Nov 16:S1995-820X(23)00137-2.
doi: 10.1016/j.virs.2023.11.005. Online ahead of print. Naturally occurring PAE206K point mutation in 2009 H1N1 pandemic influenza viruses impairs viral replication at high temperatures
Mengmeng Cao 1 , Qiannan Jia 1 , Jinghua Li 1 , Lili Zhao 1 , Li Zhu 2 , Yufan Zhang 2 , Shan Li 2 , Tao Deng 3
Affiliations
The emergence of influenza virus A pandemic H1N1 in April 2009 marked the first pandemic of the 21st century. In this study, we observed significant differences in the polymerase activities of two clinical 2009 H1N1 influenza A virus isolates from Chinese and Japanese patients. Sequence comparison of the three main protein subunits (PB2, PB1, and PA) of the viral RNA-dependent RNA polymerase complex and subsequent mutational analysis revealed that a single amino acid substitution (E206K) was responsible for the observed impaired replication phenotype. Further in vitro experiments showed that presence of PAE206K decreased the replication of influenza A/WSN/33 virus in mammalian cells and a reduction in the virus's pathogenicity in vivo. Mechanistic studies revealed that PAE206K is a temperature-sensitive mutant associated with the inability to transport PB1-PA complex to the nucleus at high temperatures (39.5 °C). Hence, this naturally occurring variant in the PA protein represents an ideal candidate mutation for the development of live attenuated influenza vaccines.
Keywords: H1N1; influenza A virus; point mutation; polymerase acidic protein; viral replication.
. 2023 Nov 16:S1995-820X(23)00137-2.
doi: 10.1016/j.virs.2023.11.005. Online ahead of print. Naturally occurring PAE206K point mutation in 2009 H1N1 pandemic influenza viruses impairs viral replication at high temperatures
Mengmeng Cao 1 , Qiannan Jia 1 , Jinghua Li 1 , Lili Zhao 1 , Li Zhu 2 , Yufan Zhang 2 , Shan Li 2 , Tao Deng 3
Affiliations
- PMID: 37979619
- DOI: 10.1016/j.virs.2023.11.005
The emergence of influenza virus A pandemic H1N1 in April 2009 marked the first pandemic of the 21st century. In this study, we observed significant differences in the polymerase activities of two clinical 2009 H1N1 influenza A virus isolates from Chinese and Japanese patients. Sequence comparison of the three main protein subunits (PB2, PB1, and PA) of the viral RNA-dependent RNA polymerase complex and subsequent mutational analysis revealed that a single amino acid substitution (E206K) was responsible for the observed impaired replication phenotype. Further in vitro experiments showed that presence of PAE206K decreased the replication of influenza A/WSN/33 virus in mammalian cells and a reduction in the virus's pathogenicity in vivo. Mechanistic studies revealed that PAE206K is a temperature-sensitive mutant associated with the inability to transport PB1-PA complex to the nucleus at high temperatures (39.5 °C). Hence, this naturally occurring variant in the PA protein represents an ideal candidate mutation for the development of live attenuated influenza vaccines.
Keywords: H1N1; influenza A virus; point mutation; polymerase acidic protein; viral replication.