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  • SARS-CoV-2 spike protein dictates syncytium-mediated lymphocyte elimination #MMPMID33879858
  • Zhang Z; Zheng Y; Niu Z; Zhang B; Wang C; Yao X; Peng H; Franca DN; Wang Y; Zhu Y; Su Y; Tang M; Jiang X; Ren H; He M; Wang Y; Gao L; Zhao P; Shi H; Chen Z; Wang X; Piacentini M; Bian X; Melino G; Liu L; Huang H; Sun Q
  • Cell Death Differ 2021[Sep]; 28 (9): 2765-2777 PMID33879858show ga
  • 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.
  • |COVID-19/pathology/*virology[MESH]
  • |Cell Line[MESH]
  • |Cell Line, Tumor[MESH]
  • |Giant Cells/pathology/*virology[MESH]
  • |HEK293 Cells[MESH]
  • |HeLa Cells[MESH]
  • |Humans[MESH]
  • |Jurkat Cells[MESH]
  • |K562 Cells[MESH]
  • |Lymphocytes/pathology/*virology[MESH]
  • |SARS-CoV-2/*metabolism/*pathogenicity[MESH]
  • |Spike Glycoprotein, Coronavirus/*metabolism[MESH]
  • |Virus Internalization[MESH]
  • |Virus Replication/genetics[MESH]

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  • suck abstract from ncbi

    2765 9.28 2021