TY  - JOUR
AU  - Zhang, Zhengrong
AU  - Zheng, You
AU  - Niu, Zubiao
AU  - Zhang, Bo
AU  - Wang, Chenxi
AU  - Yao, Xiaohong
AU  - Peng, Haoran
AU  - Franca, Del Nonno
AU  - Wang, Yunyun
AU  - Zhu, Yichao
AU  - Su, Yan
AU  - Tang, Meng
AU  - Jiang, Xiaoyi
AU  - Ren, He
AU  - He, Meifang
AU  - Wang, Yuqi
AU  - Gao, Lihua
AU  - Zhao, Ping
AU  - Shi, Hanping
AU  - Chen, Zhaolie
AU  - Wang, Xiaoning
AU  - Piacentini, Mauro
AU  - Bian, Xiuwu
AU  - Melino, Gerry
AU  - Liu, Liang
AU  - Huang, Hongyan
AU  - Sun, Qiang
TI  - SARS-CoV-2 spike protein dictates syncytium-mediated lymphocyte elimination.
JO  - Cell death and differentiation
VL  - 28
IS  - 9
SN  - 1476-5403
CY  - London
PB  - Macmillan
M1  - DZNE-2021-00755
SP  - 2765-2777
PY  - 2021
AB  - 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.
KW  - COVID-19: pathology
KW  - COVID-19: virology
KW  - Cell Line
KW  - Cell Line, Tumor
KW  - Giant Cells: pathology
KW  - Giant Cells: virology
KW  - HEK293 Cells
KW  - HeLa Cells
KW  - Humans
KW  - Jurkat Cells
KW  - K562 Cells
KW  - Lymphocytes: pathology
KW  - Lymphocytes: virology
KW  - SARS-CoV-2: metabolism
KW  - SARS-CoV-2: pathogenicity
KW  - Spike Glycoprotein, Coronavirus: metabolism
KW  - Virus Internalization
KW  - Virus Replication: genetics
LB  - PUB:(DE-HGF)16
C6  - pmid:33879858
C2  - pmc:PMC8056997
DO  - DOI:10.1038/s41418-021-00782-3
UR  - https://pub.dzne.de/record/155577
ER  -