Spike substitution T813S increases Sarbecovirus fusogenicity by enhancing the usage of TMPRSS2.
SARS-CoV Spike (S) protein shares considerable homology with SARS-CoV-2 S, especially in the conserved S2 subunit (S2). S protein mediates coronavirus receptor binding and membrane fusion, and the latter activity can greatly influence coronavirus infection. We observed that SARS-CoV S is less effect...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2023-05-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1011123 |
| _version_ | 1827932850341543936 |
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| author | Yong Ma Pengbin Li Yunqi Hu Tianyi Qiu Lixiang Wang Hongjie Lu Kexin Lv Mengxin Xu Jiaxin Zhuang Xue Liu Suhua He Bing He Shuning Liu Lin Liu Yuanyuan Wang Xinyu Yue Yanmei Zhai Wanyu Luo Haoting Mai Yu Kuang Shifeng Chen Feng Ye Na Zhou Wenjing Zhao Jun Chen Shoudeng Chen Xiaoli Xiong Mang Shi Ji-An Pan Yao-Qing Chen |
| author_facet | Yong Ma Pengbin Li Yunqi Hu Tianyi Qiu Lixiang Wang Hongjie Lu Kexin Lv Mengxin Xu Jiaxin Zhuang Xue Liu Suhua He Bing He Shuning Liu Lin Liu Yuanyuan Wang Xinyu Yue Yanmei Zhai Wanyu Luo Haoting Mai Yu Kuang Shifeng Chen Feng Ye Na Zhou Wenjing Zhao Jun Chen Shoudeng Chen Xiaoli Xiong Mang Shi Ji-An Pan Yao-Qing Chen |
| author_sort | Yong Ma |
| collection | DOAJ |
| description | SARS-CoV Spike (S) protein shares considerable homology with SARS-CoV-2 S, especially in the conserved S2 subunit (S2). S protein mediates coronavirus receptor binding and membrane fusion, and the latter activity can greatly influence coronavirus infection. We observed that SARS-CoV S is less effective in inducing membrane fusion compared with SARS-CoV-2 S. We identify that S813T mutation is sufficient in S2 interfering with the cleavage of SARS-CoV-2 S by TMPRSS2, reducing spike fusogenicity and pseudoparticle entry. Conversely, the mutation of T813S in SARS-CoV S increased fusion ability and viral replication. Our data suggested that residue 813 in the S was critical for the proteolytic activation, and the change from threonine to serine at 813 position might be an evolutionary feature adopted by SARS-2-related viruses. This finding deepened the understanding of Spike fusogenicity and could provide a new perspective for exploring Sarbecovirus' evolution. |
| first_indexed | 2024-03-13T07:16:12Z |
| format | Article |
| id | doaj.art-95aee3d13ff44bb386b2f64395fc8428 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-03-13T07:16:12Z |
| publishDate | 2023-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-95aee3d13ff44bb386b2f64395fc84282023-06-05T05:31:45ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742023-05-01195e101112310.1371/journal.ppat.1011123Spike substitution T813S increases Sarbecovirus fusogenicity by enhancing the usage of TMPRSS2.Yong MaPengbin LiYunqi HuTianyi QiuLixiang WangHongjie LuKexin LvMengxin XuJiaxin ZhuangXue LiuSuhua HeBing HeShuning LiuLin LiuYuanyuan WangXinyu YueYanmei ZhaiWanyu LuoHaoting MaiYu KuangShifeng ChenFeng YeNa ZhouWenjing ZhaoJun ChenShoudeng ChenXiaoli XiongMang ShiJi-An PanYao-Qing ChenSARS-CoV Spike (S) protein shares considerable homology with SARS-CoV-2 S, especially in the conserved S2 subunit (S2). S protein mediates coronavirus receptor binding and membrane fusion, and the latter activity can greatly influence coronavirus infection. We observed that SARS-CoV S is less effective in inducing membrane fusion compared with SARS-CoV-2 S. We identify that S813T mutation is sufficient in S2 interfering with the cleavage of SARS-CoV-2 S by TMPRSS2, reducing spike fusogenicity and pseudoparticle entry. Conversely, the mutation of T813S in SARS-CoV S increased fusion ability and viral replication. Our data suggested that residue 813 in the S was critical for the proteolytic activation, and the change from threonine to serine at 813 position might be an evolutionary feature adopted by SARS-2-related viruses. This finding deepened the understanding of Spike fusogenicity and could provide a new perspective for exploring Sarbecovirus' evolution.https://doi.org/10.1371/journal.ppat.1011123 |
| spellingShingle | Yong Ma Pengbin Li Yunqi Hu Tianyi Qiu Lixiang Wang Hongjie Lu Kexin Lv Mengxin Xu Jiaxin Zhuang Xue Liu Suhua He Bing He Shuning Liu Lin Liu Yuanyuan Wang Xinyu Yue Yanmei Zhai Wanyu Luo Haoting Mai Yu Kuang Shifeng Chen Feng Ye Na Zhou Wenjing Zhao Jun Chen Shoudeng Chen Xiaoli Xiong Mang Shi Ji-An Pan Yao-Qing Chen Spike substitution T813S increases Sarbecovirus fusogenicity by enhancing the usage of TMPRSS2. PLoS Pathogens |
| title | Spike substitution T813S increases Sarbecovirus fusogenicity by enhancing the usage of TMPRSS2. |
| title_full | Spike substitution T813S increases Sarbecovirus fusogenicity by enhancing the usage of TMPRSS2. |
| title_fullStr | Spike substitution T813S increases Sarbecovirus fusogenicity by enhancing the usage of TMPRSS2. |
| title_full_unstemmed | Spike substitution T813S increases Sarbecovirus fusogenicity by enhancing the usage of TMPRSS2. |
| title_short | Spike substitution T813S increases Sarbecovirus fusogenicity by enhancing the usage of TMPRSS2. |
| title_sort | spike substitution t813s increases sarbecovirus fusogenicity by enhancing the usage of tmprss2 |
| url | https://doi.org/10.1371/journal.ppat.1011123 |
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