tetano
Editor, Senior Moderator
Cell Death Differ
. 2021 Apr 20.
doi: 10.1038/s41418-021-00782-3. Online ahead of print.
SARS-CoV-2 spike protein dictates syncytium-mediated lymphocyte elimination
Zhengrong Zhang[SUP] #[/SUP][SUP] 1 2 [/SUP], You Zheng[SUP] #[/SUP][SUP] 1 [/SUP], Zubiao Niu[SUP] #[/SUP][SUP] 1 [/SUP], Bo Zhang[SUP] #[/SUP][SUP] 1 2 [/SUP], Chenxi Wang[SUP] #[/SUP][SUP] 1 [/SUP], Xiaohong Yao[SUP] #[/SUP][SUP] 3 [/SUP], Haoran Peng[SUP] 4 [/SUP], Del Nonno Franca[SUP] 5 [/SUP], Yunyun Wang[SUP] 6 [/SUP], Yichao Zhu[SUP] 1 [/SUP], Yan Su[SUP] 1 [/SUP], Meng Tang[SUP] 1 2 [/SUP], Xiaoyi Jiang[SUP] 1 2 [/SUP], He Ren[SUP] 1 2 [/SUP], Meifang He[SUP] 7 [/SUP], Yuqi Wang[SUP] 1 [/SUP], Lihua Gao[SUP] 1 [/SUP], Ping Zhao[SUP] 4 [/SUP], Hanping Shi[SUP] 2 [/SUP], Zhaolie Chen[SUP] 1 [/SUP], Xiaoning Wang[SUP] 8 9 [/SUP], Mauro Piacentini[SUP] 5 10 [/SUP], Xiuwu Bian[SUP] 3 [/SUP], Gerry Melino[SUP] 11 12 [/SUP], Liang Liu[SUP] 13 [/SUP], Hongyan Huang[SUP] 14 [/SUP], Qiang Sun[SUP] 15 16 [/SUP]
Affiliations
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 (~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.
. 2021 Apr 20.
doi: 10.1038/s41418-021-00782-3. Online ahead of print.
SARS-CoV-2 spike protein dictates syncytium-mediated lymphocyte elimination
Zhengrong Zhang[SUP] #[/SUP][SUP] 1 2 [/SUP], You Zheng[SUP] #[/SUP][SUP] 1 [/SUP], Zubiao Niu[SUP] #[/SUP][SUP] 1 [/SUP], Bo Zhang[SUP] #[/SUP][SUP] 1 2 [/SUP], Chenxi Wang[SUP] #[/SUP][SUP] 1 [/SUP], Xiaohong Yao[SUP] #[/SUP][SUP] 3 [/SUP], Haoran Peng[SUP] 4 [/SUP], Del Nonno Franca[SUP] 5 [/SUP], Yunyun Wang[SUP] 6 [/SUP], Yichao Zhu[SUP] 1 [/SUP], Yan Su[SUP] 1 [/SUP], Meng Tang[SUP] 1 2 [/SUP], Xiaoyi Jiang[SUP] 1 2 [/SUP], He Ren[SUP] 1 2 [/SUP], Meifang He[SUP] 7 [/SUP], Yuqi Wang[SUP] 1 [/SUP], Lihua Gao[SUP] 1 [/SUP], Ping Zhao[SUP] 4 [/SUP], Hanping Shi[SUP] 2 [/SUP], Zhaolie Chen[SUP] 1 [/SUP], Xiaoning Wang[SUP] 8 9 [/SUP], Mauro Piacentini[SUP] 5 10 [/SUP], Xiuwu Bian[SUP] 3 [/SUP], Gerry Melino[SUP] 11 12 [/SUP], Liang Liu[SUP] 13 [/SUP], Hongyan Huang[SUP] 14 [/SUP], Qiang Sun[SUP] 15 16 [/SUP]
Affiliations
- PMID: 33879858
- DOI: 10.1038/s41418-021-00782-3
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 (~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.