Home > Publications Database > SARS-CoV-2 spike protein dictates syncytium-mediated lymphocyte elimination. > print

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024 7 _ |a 10.1038/s41418-021-00782-3
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037 _ _ |a DZNE-2021-00755
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Zhang, Zhengrong
|b 0
245 _ _ |a SARS-CoV-2 spike protein dictates syncytium-mediated lymphocyte elimination.
260 _ _ |a London
|c 2021
|b Macmillan
336 7 _ |a article
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336 7 _ |a ARTICLE
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520 _ _ |a 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.
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650 _ 2 |a COVID-19: pathology
|2 MeSH
650 _ 2 |a COVID-19: virology
|2 MeSH
650 _ 2 |a Cell Line
|2 MeSH
650 _ 2 |a Cell Line, Tumor
|2 MeSH
650 _ 2 |a Giant Cells: pathology
|2 MeSH
650 _ 2 |a Giant Cells: virology
|2 MeSH
650 _ 2 |a HEK293 Cells
|2 MeSH
650 _ 2 |a HeLa Cells
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Jurkat Cells
|2 MeSH
650 _ 2 |a K562 Cells
|2 MeSH
650 _ 2 |a Lymphocytes: pathology
|2 MeSH
650 _ 2 |a Lymphocytes: virology
|2 MeSH
650 _ 2 |a SARS-CoV-2: metabolism
|2 MeSH
650 _ 2 |a SARS-CoV-2: pathogenicity
|2 MeSH
650 _ 2 |a Spike Glycoprotein, Coronavirus: metabolism
|2 MeSH
650 _ 2 |a Virus Internalization
|2 MeSH
650 _ 2 |a Virus Replication: genetics
|2 MeSH
700 1 _ |a Zheng, You
|b 1
700 1 _ |a Niu, Zubiao
|b 2
700 1 _ |a Zhang, Bo
|b 3
700 1 _ |a Wang, Chenxi
|b 4
700 1 _ |a Yao, Xiaohong
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700 1 _ |a Peng, Haoran
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700 1 _ |a Franca, Del Nonno
|b 7
700 1 _ |a Wang, Yunyun
|b 8
700 1 _ |a Zhu, Yichao
|b 9
700 1 _ |a Su, Yan
|b 10
700 1 _ |a Tang, Meng
|b 11
700 1 _ |a Jiang, Xiaoyi
|b 12
700 1 _ |a Ren, He
|b 13
700 1 _ |a He, Meifang
|b 14
700 1 _ |a Wang, Yuqi
|b 15
700 1 _ |a Gao, Lihua
|b 16
700 1 _ |a Zhao, Ping
|b 17
700 1 _ |a Shi, Hanping
|b 18
700 1 _ |a Chen, Zhaolie
|b 19
700 1 _ |a Wang, Xiaoning
|b 20
700 1 _ |a Piacentini, Mauro
|b 21
700 1 _ |a Bian, Xiuwu
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700 1 _ |a Melino, Gerry
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|u dzne
700 1 _ |a Liu, Liang
|b 24
700 1 _ |a Huang, Hongyan
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700 1 _ |a Sun, Qiang
|0 0000-0001-8094-2214
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|e Corresponding author
773 _ _ |a 10.1038/s41418-021-00782-3
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856 4 _ |u https://www.nature.com/articles/s41418-021-00782-3
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910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
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914 1 _ |y 2021
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