Abstract
In cultured cells, SARS-CoV-2 infects cells via multiple pathways using different host proteases. Recent studies have shown that the furin and TMPRSS2 (furin/TMPRSS2)-dependent pathway plays a minor role in infection of the Omicron variant. Here, we confirm that Omicron uses the furin/TMPRSS2-dependent pathway inefficiently and enters cells mainly using the cathepsin-dependent endocytosis pathway in TMPRSS2-expressing VeroE6/TMPRSS2 and Calu-3 cells. This is the case despite efficient cleavage of the spike protein of Omicron. However, in the airways of TMPRSS2-knockout mice, Omicron infection is significantly reduced. We furthermore show that propagation of the mouse-adapted SARS-CoV-2 QHmusX strain and human clinical isolates of Beta and Gamma is reduced in TMPRSS2-knockout mice. Therefore, the Omicron variant isn’t an exception in using TMPRSS2 in vivo, and analysis with TMPRSS2-knockout mice is important when evaluating SARS-CoV-2 variants. In conclusion, this study shows that TMPRSS2 is critically important for SARS-CoV-2 infection of murine airways, including the Omicron variant.
【초록키워드】 SARS-CoV-2, TMPRSS2, furin, SARS-COV-2 infection, variant, Infection, omicron, airway, SARS-CoV-2 variants, mice, pathway, Gamma, cleavage, Beta, in vivo, Analysis, host proteases, calu-3 cells, mouse-adapted SARS-CoV-2, airways, cultured cells, infect, murine, isolate, recent, Cell, shown, significantly, reduced, the spike protein, cathepsin-dependent, multiple pathway, 【제목키워드】 TMPRSS2, SARS-COV-2 infection, airway, murine, Essential,