%0 Journal Article
%A Zhang, Zhengrong
%A Zheng, You
%A Niu, Zubiao
%A Zhang, Bo
%A Wang, Chenxi
%A Yao, Xiaohong
%A Peng, Haoran
%A Franca, Del Nonno
%A Wang, Yunyun
%A Zhu, Yichao
%A Su, Yan
%A Tang, Meng
%A Jiang, Xiaoyi
%A Ren, He
%A He, Meifang
%A Wang, Yuqi
%A Gao, Lihua
%A Zhao, Ping
%A Shi, Hanping
%A Chen, Zhaolie
%A Wang, Xiaoning
%A Piacentini, Mauro
%A Bian, Xiuwu
%A Melino, Gerry
%A Liu, Liang
%A Huang, Hongyan
%A Sun, Qiang
%T SARS-CoV-2 spike protein dictates syncytium-mediated lymphocyte elimination.
%J Cell death and differentiation
%V 28
%N 9
%@ 1476-5403
%C London
%I Macmillan
%M DZNE-2021-00755
%P 2765-2777
%D 2021
%X 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 ( 45.1 nm/s) 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.
%K COVID-19: pathology
%K COVID-19: virology
%K Cell Line
%K Cell Line, Tumor
%K Giant Cells: pathology
%K Giant Cells: virology
%K HEK293 Cells
%K HeLa Cells
%K Humans
%K Jurkat Cells
%K K562 Cells
%K Lymphocytes: pathology
%K Lymphocytes: virology
%K SARS-CoV-2: metabolism
%K SARS-CoV-2: pathogenicity
%K Spike Glycoprotein, Coronavirus: metabolism
%K Virus Internalization
%K Virus Replication: genetics
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:33879858
%2 pmc:PMC8056997
%R 10.1038/s41418-021-00782-3
%U https://pub.dzne.de/record/155577