SARS-CoV-2 N protein mediates intercellular nucleic acid dispersion, a feature reduced in Omicron
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 expres...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-02-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S258900422300072X |
| _version_ | 1797903401401450496 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Jung-Lin Wu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-10T09:31:18Z |
| format | Article |
| id | doaj.art-bec859294c434259bd669207d2ebbff9 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-10T09:31:18Z |
| publishDate | 2023-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-bec859294c434259bd669207d2ebbff92023-02-19T04:26:52ZengElsevieriScience2589-00422023-02-01262105995SARS-CoV-2 N protein mediates intercellular nucleic acid dispersion, a feature reduced in OmicronJung-Lin Wu0I.-I. Kuan1Jing-You Guo2Wei-Chia Hsu3Wei-Chun Tang4Hsin-Ju Chan5Yu-Ju Chen6Bi-Chang Chen7Han-Chung Wu8James C. Liao9Institute of Biological Chemistry, Academia Sinica, Taipei 115, TaiwanInstitute of Biological Chemistry, Academia Sinica, Taipei 115, TaiwanInstitute of Biological Chemistry, Academia Sinica, Taipei 115, TaiwanInstitute of Biological Chemistry, Academia Sinica, Taipei 115, TaiwanResearch Center for Applied Sciences, Academia Sinica, Taipei 115, TaiwanInstitute of Chemistry, Academia Sinica, Taipei 115, Taiwan; Department of Chemistry, National Taiwan University, Taipei 10617, TaiwanInstitute of Chemistry, Academia Sinica, Taipei 115, TaiwanResearch Center for Applied Sciences, Academia Sinica, Taipei 115, TaiwanInstitute of Cellular and Organismic Biology, Academia Sinica, Taipei 115, TaiwanInstitute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S258900422300072XVirologyMolecular biology |
| spellingShingle | 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 SARS-CoV-2 N protein mediates intercellular nucleic acid dispersion, a feature reduced in Omicron iScience Virology Molecular biology |
| title | SARS-CoV-2 N protein mediates intercellular nucleic acid dispersion, a feature reduced in Omicron |
| title_full | SARS-CoV-2 N protein mediates intercellular nucleic acid dispersion, a feature reduced in Omicron |
| title_fullStr | SARS-CoV-2 N protein mediates intercellular nucleic acid dispersion, a feature reduced in Omicron |
| title_full_unstemmed | SARS-CoV-2 N protein mediates intercellular nucleic acid dispersion, a feature reduced in Omicron |
| title_short | SARS-CoV-2 N protein mediates intercellular nucleic acid dispersion, a feature reduced in Omicron |
| title_sort | sars cov 2 n protein mediates intercellular nucleic acid dispersion a feature reduced in omicron |
| topic | Virology Molecular biology |
| url | http://www.sciencedirect.com/science/article/pii/S258900422300072X |
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