Beyond Stress Granules: G3BP1 and G3BP2 Redundantly Suppress SARS-CoV-2 Infection
The global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed unprecedented challenges to public health and economic stability. Central to SARS-CoV-2 pathogenesis is its ability to evade the host immune response by hijacking host pathways via the interaction be...
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MDPI AG
2025-06-01
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| author | Duo Xu Mahamaya Biswal Quanqing Zhang Christine Light Yijie Wu Chenjin Ye Luis Martínez-Sobrido Jikui Song Rong Hai |
| author_facet | Duo Xu Mahamaya Biswal Quanqing Zhang Christine Light Yijie Wu Chenjin Ye Luis Martínez-Sobrido Jikui Song Rong Hai |
| author_sort | Duo Xu |
| collection | DOAJ |
| description | The global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed unprecedented challenges to public health and economic stability. Central to SARS-CoV-2 pathogenesis is its ability to evade the host immune response by hijacking host pathways via the interaction between viral and host proteins. We identified Ras-GTPase-activating protein SH3 domain-binding protein 1/2 (G3BP1/G3BP2) as a critical host factor that interacts with the viral nucleocapsid (N) protein, emerging from a comparative analysis of proteomic data from multiple studies. We revisited the underlying molecular mechanisms by confirming the residues required for the interaction between G3BP1/G3BP2 and SARS-CoV-2 N protein and showed that this interaction disrupts stress granule formation. Intriguingly, we observed that the ablation of both G3BP1 and G3BP2 enhanced SARS-CoV-2 replication. Our data collectively supports the notion that G3BP1 and G3BP2 play a critical role in modulating the host–virus interface during SARS-CoV-2 infection, and that their multifaceted function in cellular defense extends beyond the stress granule pathway. |
| format | Article |
| id | doaj-art-d82242cc4e1a4a0db9f3ed3ad139c2ed |
| institution | DOAJ |
| issn | 1999-4915 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj-art-d82242cc4e1a4a0db9f3ed3ad139c2ed2025-08-20T03:13:58ZengMDPI AGViruses1999-49152025-06-0117791210.3390/v17070912Beyond Stress Granules: G3BP1 and G3BP2 Redundantly Suppress SARS-CoV-2 InfectionDuo Xu0Mahamaya Biswal1Quanqing Zhang2Christine Light3Yijie Wu4Chenjin Ye5Luis Martínez-Sobrido6Jikui Song7Rong Hai8Department of Microbiology and Plant Pathology, University of California-Riverside, Riverside, CA 92521, USADepartment of Biochemistry, University of California-Riverside, Riverside, CA 92521, USAInstitute for Integrative Genome Biology, Proteomics Core, University of California-Riverside, Riverside, CA 92521, USADepartment of Microbiology and Plant Pathology, University of California-Riverside, Riverside, CA 92521, USADepartment of Microbiology and Plant Pathology, University of California-Riverside, Riverside, CA 92521, USATexas Biomedical Research Institute, San Antonio, TX 78227, USATexas Biomedical Research Institute, San Antonio, TX 78227, USADepartment of Biochemistry, University of California-Riverside, Riverside, CA 92521, USADepartment of Microbiology and Plant Pathology, University of California-Riverside, Riverside, CA 92521, USAThe global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed unprecedented challenges to public health and economic stability. Central to SARS-CoV-2 pathogenesis is its ability to evade the host immune response by hijacking host pathways via the interaction between viral and host proteins. We identified Ras-GTPase-activating protein SH3 domain-binding protein 1/2 (G3BP1/G3BP2) as a critical host factor that interacts with the viral nucleocapsid (N) protein, emerging from a comparative analysis of proteomic data from multiple studies. We revisited the underlying molecular mechanisms by confirming the residues required for the interaction between G3BP1/G3BP2 and SARS-CoV-2 N protein and showed that this interaction disrupts stress granule formation. Intriguingly, we observed that the ablation of both G3BP1 and G3BP2 enhanced SARS-CoV-2 replication. Our data collectively supports the notion that G3BP1 and G3BP2 play a critical role in modulating the host–virus interface during SARS-CoV-2 infection, and that their multifaceted function in cellular defense extends beyond the stress granule pathway.https://www.mdpi.com/1999-4915/17/7/912SARS-CoV-2virus–host interplaystress granulevirulencevirus replication |
| spellingShingle | Duo Xu Mahamaya Biswal Quanqing Zhang Christine Light Yijie Wu Chenjin Ye Luis Martínez-Sobrido Jikui Song Rong Hai Beyond Stress Granules: G3BP1 and G3BP2 Redundantly Suppress SARS-CoV-2 Infection Viruses SARS-CoV-2 virus–host interplay stress granule virulence virus replication |
| title | Beyond Stress Granules: G3BP1 and G3BP2 Redundantly Suppress SARS-CoV-2 Infection |
| title_full | Beyond Stress Granules: G3BP1 and G3BP2 Redundantly Suppress SARS-CoV-2 Infection |
| title_fullStr | Beyond Stress Granules: G3BP1 and G3BP2 Redundantly Suppress SARS-CoV-2 Infection |
| title_full_unstemmed | Beyond Stress Granules: G3BP1 and G3BP2 Redundantly Suppress SARS-CoV-2 Infection |
| title_short | Beyond Stress Granules: G3BP1 and G3BP2 Redundantly Suppress SARS-CoV-2 Infection |
| title_sort | beyond stress granules g3bp1 and g3bp2 redundantly suppress sars cov 2 infection |
| topic | SARS-CoV-2 virus–host interplay stress granule virulence virus replication |
| url | https://www.mdpi.com/1999-4915/17/7/912 |
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