SARS-CoV-2 N protein mediates intercellular nucleic acid dispersion, a feature reduced in Omicron.
iScience
; 26(2): 105995, 2023 Feb 17.
Article
in English
| MEDLINE | ID: covidwho-2179849
ABSTRACT
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Type of study:
Observational study
/
Prognostic study
Topics:
Variants
Language:
English
Journal:
IScience
Year:
2023
Document Type:
Article
Affiliation country:
J.isci.2023.105995
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