tetano
Editor, Senior Moderator
PLoS Pathog
. 2023 May 17;19(5):e1011123.
doi: 10.1371/journal.ppat.1011123. Online ahead of print. Spike substitution T813S increases Sarbecovirus fusogenicity by enhancing the usage of TMPRSS2
Yong Ma[SUP] 1 [/SUP], Pengbin Li[SUP] 1 [/SUP], Yunqi Hu[SUP] 1 [/SUP], Tianyi Qiu[SUP] 2 [/SUP], Lixiang Wang[SUP] 3 [/SUP], Hongjie Lu[SUP] 1 [/SUP], Kexin Lv[SUP] 1 [/SUP], Mengxin Xu[SUP] 1 [/SUP], Jiaxin Zhuang[SUP] 4 [/SUP], Xue Liu[SUP] 4 [/SUP], Suhua He[SUP] 5 [/SUP], Bing He[SUP] 1 [/SUP], Shuning Liu[SUP] 1 [/SUP], Lin Liu[SUP] 1 [/SUP], Yuanyuan Wang[SUP] 1 [/SUP], Xinyu Yue[SUP] 1 [/SUP], Yanmei Zhai[SUP] 1 [/SUP], Wanyu Luo[SUP] 1 [/SUP], Haoting Mai[SUP] 1 [/SUP], Yu Kuang[SUP] 1 [/SUP], Shifeng Chen[SUP] 6 [/SUP], Feng Ye[SUP] 6 [/SUP], Na Zhou[SUP] 6 [/SUP], Wenjing Zhao[SUP] 4 [/SUP], Jun Chen[SUP] 3 [/SUP], Shoudeng Chen[SUP] 5 [/SUP], Xiaoli Xiong[SUP] 7 [/SUP], Mang Shi[SUP] 4 [/SUP], Ji-An Pan[SUP] 4 [/SUP], Yao-Qing Chen[SUP] 1 8 [/SUP]
Affiliations
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.
. 2023 May 17;19(5):e1011123.
doi: 10.1371/journal.ppat.1011123. Online ahead of print. Spike substitution T813S increases Sarbecovirus fusogenicity by enhancing the usage of TMPRSS2
Yong Ma[SUP] 1 [/SUP], Pengbin Li[SUP] 1 [/SUP], Yunqi Hu[SUP] 1 [/SUP], Tianyi Qiu[SUP] 2 [/SUP], Lixiang Wang[SUP] 3 [/SUP], Hongjie Lu[SUP] 1 [/SUP], Kexin Lv[SUP] 1 [/SUP], Mengxin Xu[SUP] 1 [/SUP], Jiaxin Zhuang[SUP] 4 [/SUP], Xue Liu[SUP] 4 [/SUP], Suhua He[SUP] 5 [/SUP], Bing He[SUP] 1 [/SUP], Shuning Liu[SUP] 1 [/SUP], Lin Liu[SUP] 1 [/SUP], Yuanyuan Wang[SUP] 1 [/SUP], Xinyu Yue[SUP] 1 [/SUP], Yanmei Zhai[SUP] 1 [/SUP], Wanyu Luo[SUP] 1 [/SUP], Haoting Mai[SUP] 1 [/SUP], Yu Kuang[SUP] 1 [/SUP], Shifeng Chen[SUP] 6 [/SUP], Feng Ye[SUP] 6 [/SUP], Na Zhou[SUP] 6 [/SUP], Wenjing Zhao[SUP] 4 [/SUP], Jun Chen[SUP] 3 [/SUP], Shoudeng Chen[SUP] 5 [/SUP], Xiaoli Xiong[SUP] 7 [/SUP], Mang Shi[SUP] 4 [/SUP], Ji-An Pan[SUP] 4 [/SUP], Yao-Qing Chen[SUP] 1 8 [/SUP]
Affiliations
- PMID: 37196033
- DOI: 10.1371/journal.ppat.1011123
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.