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:
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