Essential role of TMPRSS2 in SARS-CoV-2 infection in murine airways
In: Nature communications, Jg. 13 (2022-04-13), Heft 1
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Zugriff:
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.
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Essential role of TMPRSS2 in SARS-CoV-2 infection in murine airways
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Autor/in / Beteiligte Person: | 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 |
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Zeitschrift: | Nature communications, Jg. 13 (2022-04-13), Heft 1 |
Veröffentlichung: | 2022 |
Medientyp: | unknown |
ISSN: | 2041-1723 (print) |
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