The respective roles of TMPRSS2 and cathepsins for SARS-CoV-2 infection in human respiratory organoids
We explored how the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus infects human respiratory organoids, which are a cultured cell model made to mimic the physiological conditions of the human airways. We focused on understanding the role of different proteases of host cells in activating the virus spike proteins. Specifically, we looked at TMPRSS2, a transmembrane serine protease, and cathepsin L, a lysosomal enzyme, which helps the virus enter cells by cutting the viral spike protein. We discovered that while TMPRSS2 is crucial for the virus in certain cells and animal models, other proteases, including cathepsins and various serine proteases, also play significant roles in the SARS-CoV-2 infection of human respiratory organoids. We suggest that SARS-CoV-2 uses a more complex mechanism involving multiple proteases to infect human airways, differing from what we see in conventional cell lines or animal models. This complexity might help explain how different variants can spread and infect people effectively.
Authors
- Takuya Yamamoto (ORCID: https://orcid.org/0000-0002-0022-3947)
- Masatoshi Kakizaki (ORCID: https://orcid.org/0000-0002-9388-8402)
- Rina Hashimoto (ORCID: https://orcid.org/0000-0002-7174-4563)
- Yuki Kitai (ORCID: https://orcid.org/0000-0003-3271-6807)
- Akihide Ryo (ORCID: https://orcid.org/0000-0001-6028-8091)
- Takashi Okura (ORCID: https://orcid.org/0000-0002-6019-958X)
- Kazuo Takayama (ORCID: https://orcid.org/0000-0002-1132-2457)
- Makoto Takeda (ORCID: https://orcid.org/0000-0002-8194-7727)
- Noriyo Nagata (ORCID: https://orcid.org/0000-0001-9147-1438)
- Kazuya Shirato (ORCID: https://orcid.org/0000-0002-3375-9799)
- Hiroshi Katoh (ORCID: https://orcid.org/0009-0005-8327-0907)
- Yukiko Akahori
Institutions
- Kyoto University (JP)
- National Institute of Infectious Diseases (JP)
- RIKEN Center for Advanced Intelligence Project (JP)
- The University of Tokyo (JP)
Publication Details
- Journal
- Journal of Virology
- Published
- 2024-11-27
- DOI
- https://doi.org/10.1128/jvi.01853-24
- Citations
- 9
- Primary Topic
- COVID-19 Clinical Research Studies
- Type
- article
- Field-Weighted Citation Impact
- 3.50
Funders
- Japan Agency for Medical Research and Development
- Research Promotion Foundation
- Mitsubishi Foundation
- Astellas Pharma
- Shionogi
- Astellas Foundation for Research on Metabolic Disorders
- Japan Society for the Promotion of Science