SARS-CoV-2 pseudovirus enters the host cells through spike protein-CD147 in an Arf6-dependent manner. Issue 1 (31st December 2022)

• Record Type: Journal Article
• Authors: Zhou, Yun-Qi; Wang, Ke; Wang, Xue-Yan; Cui, Hong-Yong; Zhao, Yongxiang; Zhu, Ping; Chen, Zhi-Nan
• Is Part Of: Emerging microbes & infections. Volume 11:Issue 1(2022)
• Page Start: 1135
• Page End: 1144
• Publication Date: 2022-12-31
• Subjects: SARS-CoV-2 -- CD147 -- endocytosis -- Arf6 -- spike protein; Medical microbiology -- Periodicals; Communicable diseases -- Periodicals; Infection -- Periodicals; 616.9041
• DOI: 10.1080/22221751.2022.2059403
• Languages: English
• ISSNs: 2222-1751

Abstract

ABSTRACT: The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants is threatening public health around the world. Endocytosis functions as an important way for viral infection, and SARS-CoV-2 bears no exception. However, the specific endocytic mechanism of SARS-CoV-2 remains unknown. In this study, we used endocytic inhibitors to evaluate the role of different endocytic routes in SARS-CoV-2 pseudovirus infection and found that the viral infection was associated with caveolar/lipid raft- and cytoskeleton-mediated endocytosis, but independent of the clathrin-mediated endocytosis and macropinocytosis. Meanwhile, the knockdown of CD147 and Rab5a in Vero E6 and Huh-7 cells inhibited SARS-CoV-2 pseudovirus infection, and the co-localization of spike protein, CD147, and Rab5a was observed in pseudovirus-infected Vero E6 cells, which was weakened by CD147 silencing, illustrating that SARS-CoV-2 pseudovirus entered the host cells via CD147-mediated endocytosis. Additionally, Arf6 silencing markedly inhibited pseudovirus infection in Vero E6 and Huh-7 cells, while little change was observed in CD147 knockout-Vero E6 cells. This finding indicated Arf6-mediated CD147 trafficking plays a vital role in SARS-CoV-2 entry. Taken together, our findings provide new insights into the CD147-Arf6 axis in mediating SARS-CoV-2 pseudovirus entry into the host cells, and further suggest that blockade of this pathway seems to be a feasible approach to prevent the SARS-CoV-2 infection clinically.