tetano
Editor, Senior Moderator
Emerg Microbes Infect
. 2022 Mar 28;1-16.
doi: 10.1080/22221751.2022.2059403. Online ahead of print.
SARS-CoV-2 pseudovirus enters the host cells through spike protein-CD147 in Arf6-dependent manner
Yun-Qi Zhou[SUP] 1 2 [/SUP], Ke Wang[SUP] 2 [/SUP], Xue-Yan Wang[SUP] 1 2 [/SUP], Hong-Yong Cui[SUP] 2 [/SUP], Yongxiang Zhao[SUP] 1 [/SUP], Ping Zhu[SUP] 3 [/SUP], Zhi-Nan Chen[SUP] 1 2 [/SUP]
Affiliations
Abstract
The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants is threatening the 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 Rab5 was observed in pseudovirus-infected Vero E6 cells, which was weakened by CD147 silencing, illustrating that SARS-CoV-2 pseudovirus entered 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 konckout-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 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 SARS-CoV-2 infection clinically.
Keywords: Arf6; CD147; Endocytosis; SARS-CoV-2; Spike protein.
. 2022 Mar 28;1-16.
doi: 10.1080/22221751.2022.2059403. Online ahead of print.
SARS-CoV-2 pseudovirus enters the host cells through spike protein-CD147 in Arf6-dependent manner
Yun-Qi Zhou[SUP] 1 2 [/SUP], Ke Wang[SUP] 2 [/SUP], Xue-Yan Wang[SUP] 1 2 [/SUP], Hong-Yong Cui[SUP] 2 [/SUP], Yongxiang Zhao[SUP] 1 [/SUP], Ping Zhu[SUP] 3 [/SUP], Zhi-Nan Chen[SUP] 1 2 [/SUP]
Affiliations
- PMID: 35343395
- DOI: 10.1080/22221751.2022.2059403
Abstract
The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants is threatening the 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 Rab5 was observed in pseudovirus-infected Vero E6 cells, which was weakened by CD147 silencing, illustrating that SARS-CoV-2 pseudovirus entered 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 konckout-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 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 SARS-CoV-2 infection clinically.
Keywords: Arf6; CD147; Endocytosis; SARS-CoV-2; Spike protein.