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Spike substitution T813S increases Sarbecovirus fusogenicity by enhancing the usage of TMPRSS2.
Ma, Yong; Li, Pengbin; Hu, Yunqi; Qiu, Tianyi; Wang, Lixiang; Lu, Hongjie; Lv, Kexin; Xu, Mengxin; Zhuang, Jiaxin; Liu, Xue; He, Suhua; He, Bing; Liu, Shuning; Liu, Lin; Wang, Yuanyuan; Yue, Xinyu; Zhai, Yanmei; Luo, Wanyu; Mai, Haoting; Kuang, Yu; Chen, Shifeng; Ye, Feng; Zhou, Na; Zhao, Wenjing; Chen, Jun; Chen, Shoudeng; Xiong, Xiaoli; Shi, Mang; Pan, Ji-An; Chen, Yao-Qing.
  • Ma Y; School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, China.
  • Li P; School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, China.
  • Hu Y; School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, China.
  • Qiu T; Institute of Clinical Science, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
  • Wang L; Department of Immunology and Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
  • Lu H; School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, China.
  • Lv K; School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, China.
  • Xu M; School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, China.
  • Zhuang J; The Center for Infection and Immunity Study and Molecular Cancer Research Center, School of Medicine, Shenzhen Campus of Sun Yat-sen University, Shenzhen, China.
  • Liu X; The Center for Infection and Immunity Study and Molecular Cancer Research Center, School of Medicine, Shenzhen Campus of Sun Yat-sen University, Shenzhen, China.
  • He S; Molecular Imaging Center, Guangdong Provincial Key Laboratory of Biomedical Imaging, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China.
  • He B; School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, China.
  • Liu S; School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, China.
  • Liu L; School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, China.
  • Wang Y; School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, China.
  • Yue X; School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, China.
  • Zhai Y; School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, China.
  • Luo W; School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, China.
  • Mai H; School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, China.
  • Kuang Y; School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, China.
  • Chen S; The 74(th) Group Army Hospital, Guangzhou, China.
  • Ye F; The 74(th) Group Army Hospital, Guangzhou, China.
  • Zhou N; The 74(th) Group Army Hospital, Guangzhou, China.
  • Zhao W; The Center for Infection and Immunity Study and Molecular Cancer Research Center, School of Medicine, Shenzhen Campus of Sun Yat-sen University, Shenzhen, China.
  • Chen J; Department of Immunology and Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
  • Chen S; Molecular Imaging Center, Guangdong Provincial Key Laboratory of Biomedical Imaging, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China.
  • Xiong X; State Key Laboratory of Respiratory Disease, CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
  • Shi M; The Center for Infection and Immunity Study and Molecular Cancer Research Center, School of Medicine, Shenzhen Campus of Sun Yat-sen University, Shenzhen, China.
  • Pan JA; The Center for Infection and Immunity Study and Molecular Cancer Research Center, School of Medicine, Shenzhen Campus of Sun Yat-sen University, Shenzhen, China.
  • Chen YQ; School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, China.
PLoS Pathog ; 19(5): e1011123, 2023 05.
Article Dans Anglais | MEDLINE | ID: covidwho-2324624
ABSTRACT
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.
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Texte intégral: Disponible Collection: Bases de données internationales Base de données: MEDLINE Sujet Principal: Virus du SRAS / COVID-19 Type d'étude: Étude pronostique Limites du sujet: Humains langue: Anglais Revue: PLoS Pathog Année: 2023 Type de document: Article Pays d'affiliation: Journal.ppat.1011123

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Texte intégral: Disponible Collection: Bases de données internationales Base de données: MEDLINE Sujet Principal: Virus du SRAS / COVID-19 Type d'étude: Étude pronostique Limites du sujet: Humains langue: Anglais Revue: PLoS Pathog Année: 2023 Type de document: Article Pays d'affiliation: Journal.ppat.1011123