Academic Journal
Interaction between host G3BP and viral nucleocapsid protein regulates SARS-CoV-2 replication and pathogenicity
| العنوان: | Interaction between host G3BP and viral nucleocapsid protein regulates SARS-CoV-2 replication and pathogenicity |
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| المؤلفون: | Zemin Yang, Bryan A. Johnson, Victoria A. Meliopoulos, Xiaohui Ju, Peipei Zhang, Michael P. Hughes, Jinjun Wu, Kaitlin P. Koreski, Jemma E. Clary, Ti-Cheng Chang, Gang Wu, Jeff Hixon, Jay Duffner, Kathy Wong, Rene Lemieux, Kumari G. Lokugamage, R. Elias Alvarado, Patricia A. Crocquet-Valdes, David H. Walker, Kenneth S. Plante, Jessica A. Plante, Scott C. Weaver, Hong Joo Kim, Rachel Meyers, Stacey Schultz-Cherry, Qiang Ding, Vineet D. Menachery, J. Paul Taylor |
| المصدر: | Cell Reports, Vol 43, Iss 3, Pp 113965- (2024) |
| بيانات النشر: | Elsevier, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Biology (General) |
| مصطلحات موضوعية: | CP: Microbiology, Biology (General), QH301-705.5 |
| الوصف: | Summary: G3BP1/2 are paralogous proteins that promote stress granule formation in response to cellular stresses, including viral infection. The nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inhibits stress granule assembly and interacts with G3BP1/2 via an ITFG motif, including residue F17, in the N protein. Prior studies examining the impact of the G3PB1-N interaction on SARS-CoV-2 replication have produced inconsistent findings, and the role of this interaction in pathogenesis is unknown. Here, we use structural and biochemical analyses to define the residues required for G3BP1-N interaction and structure-guided mutagenesis to selectively disrupt this interaction. We find that N-F17A mutation causes highly specific loss of interaction with G3BP1/2. SARS-CoV-2 N-F17A fails to inhibit stress granule assembly in cells, has decreased viral replication, and causes decreased pathology in vivo. Further mechanistic studies indicate that the N-F17-mediated G3BP1-N interaction promotes infection by limiting sequestration of viral genomic RNA (gRNA) into stress granules. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2211-1247 75628546 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S2211124724002936; https://doaj.org/toc/2211-1247 |
| DOI: | 10.1016/j.celrep.2024.113965 |
| URL الوصول: | https://doaj.org/article/34285ee87dee48f994909c7562854676 |
| رقم الانضمام: | edsdoj.34285ee87dee48f994909c7562854676 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 22111247 75628546 |
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| DOI: | 10.1016/j.celrep.2024.113965 |