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.
Keywords: Arf6; CD147; SARS-CoV-2; endocytosis; spike protein.
【저자키워드】 SARS-CoV-2, endocytosis, CD147, spike protein., Arf6, 【초록키워드】 public health, viral infection, coronavirus, SARS-COV-2 infection, variant, Infection, severe acute respiratory syndrome Coronavirus, endocytosis, Spike protein, CD147, Spread, cells, pseudovirus, pathway, VERO E6 cells, SARS-CoV-2 pseudovirus, inhibitor, Localization, function, Clathrin-mediated endocytosis, Arf6, Vero E6, independent of, host cells, host cell, acute respiratory syndrome, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, SARS-CoV-2 entry, blockade, Huh-7 cells, knockdown, pseudovirus infection, SARS-CoV-2 pseudovirus infection, infected Vero E6 cells, clathrin, RAB5A, approach, Prevent, independent, weakened, macropinocytosis, evaluate, indicated, clinically, inhibited, feasible, Huh-7 cell, endocytic, endocytic mechanism, the SARS-CoV-2, 【제목키워드】 host cell,