Nature communications · 2022
Essential role of TMPRSS2 in SARS-CoV-2 infection in murine airways.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Iwata-Yoshikawa Naoko, Kakizaki Masatoshi, Shiwa-Sudo Nozomi, Okura Takashi, Tahara Maino, Fukushi Shuetsu, Maeda Ken, Kawase Miyuki, Asanuma Hideki, Tomita Yuriko, Takayama Ikuyo, Matsuyama Shutoku, Shirato Kazuya, Suzuki Tadaki, Nagata Noriyo, Takeda Makoto
Аннотация
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.