Interaction between host G3BP and viral nucleocapsid protein regulates SARS-CoV-2 replication
Interaction between host G3BP and viral nucleocapsid protein regulates SARS-CoV-2 replication
Abstract G3BP1/2 are paralogous proteins that promote stress granule formation in response to cellular stresses, including viral infection. G3BP1/2 are prominent interactors of the nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the functional consequences of the G3BP1-N interaction in the context of viral infection remain unclear. Here we used structural and biochemical analyses to define the residues required for G3BP1-N interaction, followed by structure-guided mutagenesis of G3BP1 and N to selectively and reciprocally disrupt their interaction. We found that mutation of F17 within the N protein led to selective loss of interaction with G3BP1 and consequent failure of the N protein to disrupt stress granule assembly. Introduction of SARS-CoV-2 bearing an F17A mutation resulted in a significant decrease in viral replication and pathogenesis in vivo, indicating that the G3BP1-N interaction promotes infection by suppressing the ability of G3BP1 to form stress granules.
Alvardo Rojelio E.、Crocquet-Valdes Patricia A.、Walker David H.、Meyers Rachel、Ding Qiang、Taylor J. Paul、Yang Zemin、Meliopoulos Victoria A.、Wu Jinjun、Hixon Jeff、Lokugamage Kumari G.、Lemieux Rene、Plante Kenneth S.、Wu Gang、Chang Ti-Cheng、Johnson Bryan A.、Koreski Kaitlin P.、Wong Kathy、Kim Hong Joo、Schultz-Cherry Stacey、Zhang Peipei、Plante Jessica A.、Hughes Michael P.、Weaver Scott C.、Duffner Jay、Ju Xiaohui、Menachery Vineet D.
Department of Microbiology and Immunology, University of Texas Medical BranchDepartment of Pathology, University of Texas Medical BranchDepartment of Pathology, University of Texas Medical BranchFaze MedicinesSchool of Medicine, Tsinghua UniversityDepartment of Cell and Molecular Biology, St. Jude Children?ˉs Research HospitalDepartment of Cell and Molecular Biology, St. Jude Children?ˉs Research HospitalDepartment of Infectious Diseases, St. Jude Children?ˉs Research HospitalDepartment of Cell and Molecular Biology, St. Jude Children?ˉs Research HospitalFaze MedicinesDepartment of Microbiology and Immunology, University of Texas Medical BranchFaze MedicinesWorld Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical BranchCenter for Applied Bioinformatics, St. Jude Children?ˉs Research HospitalCenter for Applied Bioinformatics, St. Jude Children?ˉs Research HospitalDepartment of Microbiology and Immunology, University of Texas Medical BranchDepartment of Cell and Molecular Biology, St. Jude Children?ˉs Research HospitalFaze MedicinesDepartment of Cell and Molecular Biology, St. Jude Children?ˉs Research HospitalDepartment of Infectious Diseases, St. Jude Children?ˉs Research HospitalDepartment of Cell and Molecular Biology, St. Jude Children?ˉs Research HospitalWorld Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical BranchDepartment of Cell and Molecular Biology, St. Jude Children?ˉs Research HospitalWorld Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical BranchFaze MedicinesSchool of Medicine, Tsinghua UniversityDepartment of Microbiology and Immunology, University of Texas Medical Branch
基础医学分子生物学生物化学
Alvardo Rojelio E.,Crocquet-Valdes Patricia A.,Walker David H.,Meyers Rachel,Ding Qiang,Taylor J. Paul,Yang Zemin,Meliopoulos Victoria A.,Wu Jinjun,Hixon Jeff,Lokugamage Kumari G.,Lemieux Rene,Plante Kenneth S.,Wu Gang,Chang Ti-Cheng,Johnson Bryan A.,Koreski Kaitlin P.,Wong Kathy,Kim Hong Joo,Schultz-Cherry Stacey,Zhang Peipei,Plante Jessica A.,Hughes Michael P.,Weaver Scott C.,Duffner Jay,Ju Xiaohui,Menachery Vineet D..Interaction between host G3BP and viral nucleocapsid protein regulates SARS-CoV-2 replication[EB/OL].(2025-03-28)[2025-08-03].https://www.biorxiv.org/content/10.1101/2023.06.29.546885.点此复制
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