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000155577 037__ $$aDZNE-2021-00755
000155577 041__ $$aEnglish
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000155577 1001_ $$aZhang, Zhengrong$$b0
000155577 245__ $$aSARS-CoV-2 spike protein dictates syncytium-mediated lymphocyte elimination.
000155577 260__ $$aLondon$$bMacmillan$$c2021
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000155577 520__ $$aThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is highly contagious and causes lymphocytopenia, but the underlying mechanisms are poorly understood. We demonstrate here that heterotypic cell-in-cell structures with lymphocytes inside multinucleate syncytia are prevalent in the lung tissues of coronavirus disease 2019 (COVID-19) patients. These unique cellular structures are a direct result of SARS-CoV-2 infection, as the expression of the SARS-CoV-2 spike glycoprotein is sufficient to induce a rapid (~45.1 nm/s) membrane fusion to produce syncytium, which could readily internalize multiple lines of lymphocytes to form typical cell-in-cell structures, remarkably leading to the death of internalized cells. This membrane fusion is dictated by a bi-arginine motif within the polybasic S1/S2 cleavage site, which is frequently present in the surface glycoprotein of most highly contagious viruses. Moreover, candidate anti-viral drugs could efficiently inhibit spike glycoprotein processing, membrane fusion, and cell-in-cell formation. Together, we delineate a molecular and cellular rationale for SARS-CoV-2 pathogenesis and identify novel targets for COVID-19 therapy.
000155577 536__ $$0G:(DE-HGF)POF4-351$$a351 - Brain Function (POF4-351)$$cPOF4-351$$fPOF IV$$x0
000155577 588__ $$aDataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
000155577 650_2 $$2MeSH$$aCOVID-19: pathology
000155577 650_2 $$2MeSH$$aCOVID-19: virology
000155577 650_2 $$2MeSH$$aCell Line
000155577 650_2 $$2MeSH$$aCell Line, Tumor
000155577 650_2 $$2MeSH$$aGiant Cells: pathology
000155577 650_2 $$2MeSH$$aGiant Cells: virology
000155577 650_2 $$2MeSH$$aHEK293 Cells
000155577 650_2 $$2MeSH$$aHeLa Cells
000155577 650_2 $$2MeSH$$aHumans
000155577 650_2 $$2MeSH$$aJurkat Cells
000155577 650_2 $$2MeSH$$aK562 Cells
000155577 650_2 $$2MeSH$$aLymphocytes: pathology
000155577 650_2 $$2MeSH$$aLymphocytes: virology
000155577 650_2 $$2MeSH$$aSARS-CoV-2: metabolism
000155577 650_2 $$2MeSH$$aSARS-CoV-2: pathogenicity
000155577 650_2 $$2MeSH$$aSpike Glycoprotein, Coronavirus: metabolism
000155577 650_2 $$2MeSH$$aVirus Internalization
000155577 650_2 $$2MeSH$$aVirus Replication: genetics
000155577 7001_ $$aZheng, You$$b1
000155577 7001_ $$aNiu, Zubiao$$b2
000155577 7001_ $$aZhang, Bo$$b3
000155577 7001_ $$aWang, Chenxi$$b4
000155577 7001_ $$aYao, Xiaohong$$b5
000155577 7001_ $$aPeng, Haoran$$b6
000155577 7001_ $$aFranca, Del Nonno$$b7
000155577 7001_ $$aWang, Yunyun$$b8
000155577 7001_ $$aZhu, Yichao$$b9
000155577 7001_ $$aSu, Yan$$b10
000155577 7001_ $$aTang, Meng$$b11
000155577 7001_ $$aJiang, Xiaoyi$$b12
000155577 7001_ $$aRen, He$$b13
000155577 7001_ $$aHe, Meifang$$b14
000155577 7001_ $$aWang, Yuqi$$b15
000155577 7001_ $$aGao, Lihua$$b16
000155577 7001_ $$aZhao, Ping$$b17
000155577 7001_ $$aShi, Hanping$$b18
000155577 7001_ $$aChen, Zhaolie$$b19
000155577 7001_ $$aWang, Xiaoning$$b20
000155577 7001_ $$aPiacentini, Mauro$$b21
000155577 7001_ $$00000-0003-4383-0197$$aBian, Xiuwu$$b22
000155577 7001_ $$0P:(DE-2719)9001390$$aMelino, Gerry$$b23$$udzne
000155577 7001_ $$aLiu, Liang$$b24
000155577 7001_ $$aHuang, Hongyan$$b25
000155577 7001_ $$00000-0001-8094-2214$$aSun, Qiang$$b26$$eCorresponding author
000155577 773__ $$0PERI:(DE-600)1496681-5$$a10.1038/s41418-021-00782-3$$n9$$p2765-2777$$tCell death and differentiation$$v28$$x1476-5403$$y2021
000155577 8564_ $$uhttps://www.nature.com/articles/s41418-021-00782-3
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