期刊
CELLULAR & MOLECULAR IMMUNOLOGY
卷 19, 期 5, 页码 577-587出版社
CHIN SOCIETY IMMUNOLOGY
DOI: 10.1038/s41423-022-00845-6
关键词
COVID-19; SARS-CoV-2; neutrophil extracellular traps; histones; sialic acid
类别
资金
- National Science Foundation for Excellent Young Scholars [32122052]
- National Natural Science Foundation Regional Innovation and Development [U19A2003]
Neutrophil extracellular traps (NETs) release histones that enhance the infectivity of SARS-CoV-2 and promote cell-cell fusion. The study suggests that SARS-CoV-2 can hijack histones from NETosis to facilitate its attachment and entry into host cells.
Neutrophil extracellular traps (NETs) can capture and kill viruses, such as influenza viruses, human immunodeficiency virus (HIV), and respiratory syncytial virus (RSV), thus contributing to host defense. Contrary to our expectation, we show here that the histones released by NETosis enhance the infectivity of SARS-CoV-2, as found by using live SARS-CoV-2 and two pseudovirus systems as well as a mouse model. The histone H3 or H4 selectively binds to subunit 2 of the spike (S) protein, as shown by a biochemical binding assay, surface plasmon resonance and binding energy calculation as well as the construction of a mutant S protein by replacing four acidic amino acids. Sialic acid on the host cell surface is the key molecule to which histones bridge subunit 2 of the S protein. Moreover, histones enhance cell-cell fusion. Finally, treatment with an inhibitor of NETosis, histone H3 or H4, or sialic acid notably affected the levels of sgRNA copies and the number of apoptotic cells in a mouse model. These findings suggest that SARS-CoV-2 could hijack histones from neutrophil NETosis to promote its host cell attachment and entry process and may be important in exploring pathogenesis and possible strategies to develop new effective therapies for COVID-19.
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