Dependence of SARS-CoV-2 infection on cholesterol-rich lipid raft and endosomal acidification
| Autor: | Rikard Holmdahl, Jing Zhang, Langchong He, Yizhao Peng, Fumeng Huang, Liesu Meng, Wenhua Zhu, Shemin Lu, Lei Zhang, Meiyang Fan, Xiaowei Li, Nan Wang |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Endosome
viruses Biophysics Endocytosis Biochemistry Clathrin Virus 03 medical and health sciences 0302 clinical medicine Structural Biology Lysosome Caveolin Genetics medicine skin and connective tissue diseases Lipid raft Lipid rafts ComputingMethodologies_COMPUTERGRAPHICS 030304 developmental biology Dynamin 0303 health sciences biology SARS-CoV-2 Chemistry fungi virus diseases Virology Computer Science Applications body regions Cholesterol medicine.anatomical_structure 030220 oncology & carcinogenesis biology.protein Endosomal acidification TP248.13-248.65 Research Article Biotechnology |
| Zdroj: | Computational and Structural Biotechnology Journal Computational and Structural Biotechnology Journal, Vol 19, Iss, Pp 1933-1943 (2021) |
| ISSN: | 2001-0370 |
| Popis: | Graphical abstract Coronavirus disease 2019 is a kind of viral pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the mechanism whereby SARS-CoV-2 invades host cells remains poorly understood. Here we used SARS-CoV-2 pseudoviruses to infect human angiotensin-converting enzyme 2 (ACE2) expressing HEK293T cells and evaluated virus infection. We confirmed that SARS-CoV-2 entry was dependent on ACE2 and sensitive to pH of endosome/lysosome in HEK293T cells. The infection of SARS-CoV-2 pseudoviruses is independent of dynamin, clathrin, caveolin and endophilin A2, as well as macropinocytosis. Instead, we found that the infection of SARS-CoV-2 pseudoviruses was cholesterol-rich lipid raft dependent. Cholesterol depletion of cell membranes with methyl-β-cyclodextrin resulted in reduction of pseudovirus infection. The infection of SARS-CoV-2 pseudoviruses resumed with cholesterol supplementation. Together, cholesterol-rich lipid rafts, and endosomal acidification, are key steps of SARS-CoV-2 required for infection of host cells. Therefore, our finding expands the understanding of SARS-CoV-2 entry mechanism and provides a new anti-SARS-CoV-2 strategy. |
| Databáze: | OpenAIRE |
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