Multiple polymerase gene mutations for human adaptation occurring in Asian H5N1 influenza virus clinical isolates
Abstract The role of the influenza virus polymerase complex in host range restriction has been well-studied and several host range determinants, such as the polymerase PB2-E627K and PB2-D701N mutations, have been identified. However, there may be additional, currently unknown, human adaptation polym...
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Nature Portfolio
2018
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oai:doaj.org-article:0f3cc61631004b7ab2180d3aa419df7d2021-12-02T15:09:05ZMultiple polymerase gene mutations for human adaptation occurring in Asian H5N1 influenza virus clinical isolates10.1038/s41598-018-31397-32045-2322https://doaj.org/article/0f3cc61631004b7ab2180d3aa419df7d2018-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-31397-3https://doaj.org/toc/2045-2322Abstract The role of the influenza virus polymerase complex in host range restriction has been well-studied and several host range determinants, such as the polymerase PB2-E627K and PB2-D701N mutations, have been identified. However, there may be additional, currently unknown, human adaptation polymerase mutations. Here, we used a database search of influenza virus H5N1 clade 1.1, clade 2.3.2.1 and clade 2.3.4 strains isolated from 2008–2012 in Southern China, Vietnam and Cambodia to identify polymerase adaptation mutations that had been selected in infected patients. Several of these mutations acted either alone or together to increase viral polymerase activity in human airway cells to levels similar to the PB2-D701N and PB2-E627K single mutations and to increase progeny virus yields in infected mouse lungs to levels similar to the PB2-D701N single mutation. In particular, specific mutations acted synergistically with the PB2-D701N mutation and showed synergistic effects on viral replication both in human airway cells and mice compared with the corresponding single mutations. Thus, H5N1 viruses in infected patients were able to acquire multiple polymerase mutations that acted cooperatively for human adaptation. Our findings give new insight into the human adaptation of AI viruses and help in avian influenza virus risk assessment.Yasuha AraiNorihito KawashitaKozue HottaPhuong Vu Mai HoangHang Le Khanh NguyenThach Co NguyenCuong Duc VuongThanh Thi LeMai Thi Quynh LeKosuke SodaMadiha S. IbrahimTomo DaidojiTatsuya TakagiTatsuo ShiodaTakaaki NakayaToshihiro ItoFutoshi HasebeYohei WatanabeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-13 (2018) |
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Medicine R Science Q Yasuha Arai Norihito Kawashita Kozue Hotta Phuong Vu Mai Hoang Hang Le Khanh Nguyen Thach Co Nguyen Cuong Duc Vuong Thanh Thi Le Mai Thi Quynh Le Kosuke Soda Madiha S. Ibrahim Tomo Daidoji Tatsuya Takagi Tatsuo Shioda Takaaki Nakaya Toshihiro Ito Futoshi Hasebe Yohei Watanabe Multiple polymerase gene mutations for human adaptation occurring in Asian H5N1 influenza virus clinical isolates |
| description |
Abstract The role of the influenza virus polymerase complex in host range restriction has been well-studied and several host range determinants, such as the polymerase PB2-E627K and PB2-D701N mutations, have been identified. However, there may be additional, currently unknown, human adaptation polymerase mutations. Here, we used a database search of influenza virus H5N1 clade 1.1, clade 2.3.2.1 and clade 2.3.4 strains isolated from 2008–2012 in Southern China, Vietnam and Cambodia to identify polymerase adaptation mutations that had been selected in infected patients. Several of these mutations acted either alone or together to increase viral polymerase activity in human airway cells to levels similar to the PB2-D701N and PB2-E627K single mutations and to increase progeny virus yields in infected mouse lungs to levels similar to the PB2-D701N single mutation. In particular, specific mutations acted synergistically with the PB2-D701N mutation and showed synergistic effects on viral replication both in human airway cells and mice compared with the corresponding single mutations. Thus, H5N1 viruses in infected patients were able to acquire multiple polymerase mutations that acted cooperatively for human adaptation. Our findings give new insight into the human adaptation of AI viruses and help in avian influenza virus risk assessment. |
| format |
article |
| author |
Yasuha Arai Norihito Kawashita Kozue Hotta Phuong Vu Mai Hoang Hang Le Khanh Nguyen Thach Co Nguyen Cuong Duc Vuong Thanh Thi Le Mai Thi Quynh Le Kosuke Soda Madiha S. Ibrahim Tomo Daidoji Tatsuya Takagi Tatsuo Shioda Takaaki Nakaya Toshihiro Ito Futoshi Hasebe Yohei Watanabe |
| author_facet |
Yasuha Arai Norihito Kawashita Kozue Hotta Phuong Vu Mai Hoang Hang Le Khanh Nguyen Thach Co Nguyen Cuong Duc Vuong Thanh Thi Le Mai Thi Quynh Le Kosuke Soda Madiha S. Ibrahim Tomo Daidoji Tatsuya Takagi Tatsuo Shioda Takaaki Nakaya Toshihiro Ito Futoshi Hasebe Yohei Watanabe |
| author_sort |
Yasuha Arai |
| title |
Multiple polymerase gene mutations for human adaptation occurring in Asian H5N1 influenza virus clinical isolates |
| title_short |
Multiple polymerase gene mutations for human adaptation occurring in Asian H5N1 influenza virus clinical isolates |
| title_full |
Multiple polymerase gene mutations for human adaptation occurring in Asian H5N1 influenza virus clinical isolates |
| title_fullStr |
Multiple polymerase gene mutations for human adaptation occurring in Asian H5N1 influenza virus clinical isolates |
| title_full_unstemmed |
Multiple polymerase gene mutations for human adaptation occurring in Asian H5N1 influenza virus clinical isolates |
| title_sort |
multiple polymerase gene mutations for human adaptation occurring in asian h5n1 influenza virus clinical isolates |
| publisher |
Nature Portfolio |
| publishDate |
2018 |
| url |
https://doaj.org/article/0f3cc61631004b7ab2180d3aa419df7d |
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