tetano
Editor, Senior Moderator
iScience
. 2023 Jan 16;105995.
doi: 10.1016/j.isci.2023.105995. Online ahead of print.
SARS-CoV-2 N protein mediates intercellular nucleic acid dispersion, a feature reduced in Omicron
Jung-Lin Wu[SUP] 1 [/SUP], I-I Kuan[SUP] 1 [/SUP], Jing-You Guo[SUP] 1 [/SUP], Wei-Chia Hsu[SUP] 1 [/SUP], Wei-Chun Tang[SUP] 2 [/SUP], Hsin-Ju Chan[SUP] 3 4 [/SUP], Yu-Ju Chen[SUP] 3 [/SUP], Bi-Chang Chen[SUP] 2 [/SUP], Han-Chung Wu[SUP] 5 [/SUP], James C Liao[SUP] 1 [/SUP]
Affiliations
Abstract
The coronavirus nucleocapsid (N) protein is known to bind to nucleic acids and facilitate viral genome encapsulation. Here we report that 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 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 kinases inhibitors. Since the N-protein-mediated nucleic acid endocytosis involves a receptor commonly expressed in many types of cells, our findings suggest N protein may have an additional role in SARS-CoV-2 pathogenesis.
Keywords: COVID; Coronavirus; Omicron variant; SARS-CoV-2; nucleic acid delivery; nucleocapsid protein.
. 2023 Jan 16;105995.
doi: 10.1016/j.isci.2023.105995. Online ahead of print.
SARS-CoV-2 N protein mediates intercellular nucleic acid dispersion, a feature reduced in Omicron
Jung-Lin Wu[SUP] 1 [/SUP], I-I Kuan[SUP] 1 [/SUP], Jing-You Guo[SUP] 1 [/SUP], Wei-Chia Hsu[SUP] 1 [/SUP], Wei-Chun Tang[SUP] 2 [/SUP], Hsin-Ju Chan[SUP] 3 4 [/SUP], Yu-Ju Chen[SUP] 3 [/SUP], Bi-Chang Chen[SUP] 2 [/SUP], Han-Chung Wu[SUP] 5 [/SUP], James C Liao[SUP] 1 [/SUP]
Affiliations
- PMID: 36687314
- PMCID: PMC9841735
- DOI: 10.1016/j.isci.2023.105995
Abstract
The coronavirus nucleocapsid (N) protein is known to bind to nucleic acids and facilitate viral genome encapsulation. Here we report that 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 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 kinases inhibitors. Since the N-protein-mediated nucleic acid endocytosis involves a receptor commonly expressed in many types of cells, our findings suggest N protein may have an additional role in SARS-CoV-2 pathogenesis.
Keywords: COVID; Coronavirus; Omicron variant; SARS-CoV-2; nucleic acid delivery; nucleocapsid protein.