SARS-CoV-2 N protein mediates intercellular nucleic acid dispersion, a feature reduced in Omicron

Autor: Jung-Lin Wu, I.-I. Kuan, Jing-You Guo, Wei-Chia Hsu, Wei-Chun Tang, Hsin-Ju Chan, Yu-Ju Chen, Bi-Chang Chen, Han-Chung Wu, James C. Liao
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: iScience, Vol 26, Iss 2, Pp 105995- (2023)
Druh dokumentu: article
ISSN: 2589-0042
DOI: 10.1016/j.isci.2023.105995
Popis: Summary: The coronavirus nucleocapsid (N) protein is known to bind to nucleic acids and facilitate viral genome encapsulation. Here we report that the N protein can mediate RNA or DNA entering neighboring cells through ACE2-independent, receptor (STEAP2)-mediated endocytosis, and achieve gene expression. The effect is more pronounced for the N protein of wild-type SARS-CoV-2 than that of the Omicron variant and other human coronaviruses. This effect is enhanced by RANTES (CCL5), a chemokine induced by N protein, and lactate, a metabolite produced in hypoxia, to cause more damage. These findings might explain the clinical observations in SARS-CoV-2-infected cases. Moreover, the N protein-mediated function can be inhibited by N protein-specific monoclonal antibodies or p38 mitogen-activated protein kinase inhibitors. Since the N-protein-mediated nucleic acid endocytosis involves a receptor commonly expressed in many types of cells, our findings suggest that N protein may have an additional role in SARS-CoV-2 pathogenesis.
Databáze: Directory of Open Access Journals