1. SARS-CoV-2 Spike Protein Dictates Syncytium-mediated Lymphocyte Elimination
- Author
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Yan Su, Del Nonno Franca, Zhaolie Chen, Yunyun Wang, Hongyan Huang, Yichao Zhu, Haoran Peng, You Zheng, Lihua Gao, Bo Zhang, Xiaoning Wang, Chenxi Wang, Xiaoyi Jiang, Ping Zhao, Hanping Shi, Mauro Piacentini, Meifang He, Meng Tang, Xiu-Wu Bian, Zubiao Niu, Yuqi Wang, Xiaohong Yao, Gerry Melino, Zhengrong Zhang, He Ren, Liang Liu, and Qiang Sun
- Subjects
0301 basic medicine ,Cell biology ,virology [Lymphocytes] ,Molecular biology ,virology [COVID-19] ,viruses ,pathology [Lymphocytes] ,Biology ,Virus Replication ,Jurkat cells ,pathogenicity [SARS-CoV-2] ,Giant Cells ,Virus ,Article ,pathology [COVID-19] ,Cell Line ,metabolism [SARS-CoV-2] ,03 medical and health sciences ,virology [Giant Cells] ,Jurkat Cells ,0302 clinical medicine ,Multinucleate ,pathology [Giant Cells] ,genetics [Virus Replication] ,Cell Line, Tumor ,Humans ,ddc:610 ,Lymphocytes ,chemistry.chemical_classification ,Syncytium ,SARS-CoV-2 ,HEK 293 cells ,Lipid bilayer fusion ,COVID-19 ,Virus Internalization ,030104 developmental biology ,HEK293 Cells ,chemistry ,030220 oncology & carcinogenesis ,metabolism [Spike Glycoprotein, Coronavirus] ,Spike Glycoprotein, Coronavirus ,Glycoprotein ,K562 Cells ,K562 cells ,HeLa Cells - Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is highly contagious and causes lymphocytopenia, but the underlying mechanisms are poorly understood. We demonstrate here that heterotypic cell-in-cell structures with lymphocytes inside multinucleate syncytia are prevalent in the lung tissues of coronavirus disease 2019 (COVID-19) patients. These unique cellular structures are a direct result of SARS-CoV-2 infection, as the expression of the SARS-CoV-2 spike glycoprotein is sufficient to induce a rapid (approximately 45.1 nm/sec) membrane fusion to produce syncytium, which could readily internalize multiple lines of lymphocytes to form typical cell-in-cell structures, remarkably leading to the death of internalized cells. This membrane fusion is dictated by a bi-arginine motif within the polybasic S1/S2 cleavage site, which is frequently present in the surface glycoprotein of most highly contagious viruses. Moreover, candidate anti-viral drugs could efficiently inhibit spike glycoprotein processing, membrane fusion, and cell-in-cell formation. Together, we delineate a molecular and cellular rationale for SARS-CoV-2 pathogenesis and identify novel targets for COVID-19 therapy.
- Published
- 2021