Journal Article

DZNE-2021-00755

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png SARS-CoV-2 spike protein dictates syncytium-mediated lymphocyte elimination.

Zhang, Z. ; Zheng, Y. ; Niu, Z. ; Zhang, B. ; Wang, C. ; Yao, X. ; Peng, H. ; Franca, D. N. ; 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.DZNE* ; Liu, L. ; Huang, H. ; Sun, Q. (Corresponding author)

2021
Macmillan London

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Please use a persistent id in citations: 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.

Keyword(s): COVID-19: pathology (MeSH) ; COVID-19: virology (MeSH) ; Cell Line (MeSH) ; Cell Line, Tumor (MeSH) ; Giant Cells: pathology (MeSH) ; Giant Cells: virology (MeSH) ; HEK293 Cells (MeSH) ; HeLa Cells (MeSH) ; Humans (MeSH) ; Jurkat Cells (MeSH) ; K562 Cells (MeSH) ; Lymphocytes: pathology (MeSH) ; Lymphocytes: virology (MeSH) ; SARS-CoV-2: metabolism (MeSH) ; SARS-CoV-2: pathogenicity (MeSH) ; Spike Glycoprotein, Coronavirus: metabolism (MeSH) ; Virus Internalization (MeSH) ; Virus Replication: genetics (MeSH)

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Contributing Institute(s):

1. Synaptic Connectivity and Neurodegeneration (AG Nicotera)

Research Program(s):

1. 351 - Brain Function (POF4-351) (POF4-351)

Appears in the scientific report 2021

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 10 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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