Golgi-derived COPI vesicles fuel the biogenesis of coronavirus replication organelles.
5 affiliations
- 1Centre for Infection and Immunity Study (CIIS), School of Medicine, Shenzhen Campus of Sun Yat-sen University, Guangdong, China.
- 2State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangdong, China.
- 3Guangzhou National Laboratory, Guangdong, China.
- 4Key Laboratory of Viral Pathogenesis & Infection Prevention and Control, Jinan University, Ministry of Education, Guangdong, China.
- 5Key Laboratory of Tropical Disease Control of Ministry of Education, Institute of Human Virology, Department of Pathogen Biology and Biosecurity, Zhongshan School of Medicine, Sun Yat-sen University, Guangdong, China.
Abstract
Positive-strand RNA viruses remodel host endomembranes to form replication organelles (ROs). However, the membrane sources for coronavirus double-membrane vesicle (DMV) biogenesis remain unclear. Here, we used proteomic, genetic, pharmacological, and imaging approaches to identify the central membrane supply route for DMV formation. APEX2-based proximity proteomics first identified candidate pathways, followed by functional validation using siRNA knockdown, CRISPR/Cas9 editing, and Golgicide A (GCA) inhibition. DMV formation and viral RNA synthesis were assessed by electron microscopy, immunofluorescence, and qRT-PCR. Golgi-DMV association was analyzed by sucrose gradient fractionation and confocal imaging. In vivo relevance was evaluated in C57BL/6J mice infected with mouse hepatitis virus (MHV) and treated with GCA (intraperitoneal, 50 mg/kg; n = 4-5 per group). We showed that coronaviruses hijack the host GBF1-ARF1-COPI machinery to redirect Golgi-derived membranes to viral replication sites for DMV formation and expansion. Disruption of this pathway markedly impairs viral RNA synthesis, DMV biogenesis, and replication of multiple coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Pharmacological inhibition of Golgi-specific Brefeldin A-resistance factor 1 (GBF1) suppressed viral replication and pathology in vivo. Together, our findings reveal a previously unrecognized Golgi-derived membrane supply route for coronavirus ROs and highlight the GBF1-ARF1-COPI pathway as a potential host-directed target for broad-spectrum antiviral therapies.
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BibTeX
@article{wang2026golgiderived,
title = {{Golgi-derived COPI vesicles fuel the biogenesis of coronavirus replication organelles.}},
author = {Zhaohuan Wang and Xinyue Su and Kaoyi Gong and Zixiao Yang and Shu-Rui Liu and Bi-Rong Zheng and Keda Shi and Yu Ye and Xinrong Zhou and Jian Pan and Deyin Guo and Panpan Hou and Chun-Mei Li},
journal = {HLife},
year = {2026},
month = jul,
doi = {10.1016/j.hlife.2026.06.004},
url = {https://europepmc.org/article/MED/42903903},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Golgi-derived COPI vesicles fuel the biogenesis of coronavirus replication organelles.
AU - Zhaohuan Wang
AU - Xinyue Su
AU - Kaoyi Gong
AU - Zixiao Yang
AU - Shu-Rui Liu
AU - Bi-Rong Zheng
AU - Keda Shi
AU - Yu Ye
AU - Xinrong Zhou
AU - Jian Pan
AU - Deyin Guo
AU - Panpan Hou
AU - Chun-Mei Li
PY - 2026
DA - 2026/07/17
JO - HLife
DO - 10.1016/j.hlife.2026.06.004
UR - https://europepmc.org/article/MED/42903903
AB - Positive-strand RNA viruses remodel host endomembranes to form replication organelles (ROs). However, the membrane sources for coronavirus double-membrane vesicle (DMV) biogenesis remain unclear. Here, we used proteomic, genetic, pharmacological, and imaging approaches to identify the central membrane supply route for DMV formation. APEX2-based proximity proteomics first identified candidate pathways, followed by functional validation using siRNA knockdown, CRISPR/Cas9 editing, and Golgicide A (GCA) inhibition. DMV formation and viral RNA synthesis were assessed by electron microscopy, immunofluorescence, and qRT-PCR. Golgi-DMV association was analyzed by sucrose gradient fractionation and confocal imaging. In vivo relevance was evaluated in C57BL/6J mice infected with mouse hepatitis virus (MHV) and treated with GCA (intraperitoneal, 50 mg/kg; n = 4-5 per group). We showed that coronaviruses hijack the host GBF1-ARF1-COPI machinery to redirect Golgi-derived membranes to viral replication sites for DMV formation and expansion. Disruption of this pathway markedly impairs viral RNA synthesis, DMV biogenesis, and replication of multiple coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Pharmacological inhibition of Golgi-specific Brefeldin A-resistance factor 1 (GBF1) suppressed viral replication and pathology in vivo. Together, our findings reveal a previously unrecognized Golgi-derived membrane supply route for coronavirus ROs and highlight the GBF1-ARF1-COPI pathway as a potential host-directed target for broad-spectrum antiviral therapies.
SN - 2949-9283
ER -