TMPRSS11D and TMPRSS13 Activate the SARS-CoV-2 Spike Protein
1
Division of Molecular Pathobiology, Research Center for Zoonosis Control, Hokkaido University, N20 W10, Kita-ku, Sapporo 001-0020, Japan
2
Drug Discovery and Disease Research Laboratory, Shionogi & Co., Ltd., 3-1-1 Futaba-cho, Toyonaka, Osaka 561-0825, Japan
3
Division of Anti-Virus Drug Research, Research Center for Zoonosis Control, Hokkaido University, N20 W10, Kita-ku, Sapporo 001-0020, Japan
4
Laboratory of Biomolecular Science, Faculty of Pharmaceutical Sciences, Hokkaido University, N12 W6, Kita-ku, Sapporo 060-0812, Japan
5
National Virus Reference Laboratory, School of Medicine, University College Dublin, DO4V1W8 Dublin, Ireland
6
Centre for Research in Infectious Diseases, School of Medicine, University College Dublin, DO4V1W8 Dublin, Ireland
7
International Collaboration Unit, Research Center for Zoonosis Control, Hokkaido University, N20 W10, Kita-ku, Sapporo 001-0020, Japan
8
Global Virus Network, 725 West Lombard St, Room S413, Baltimore, MD 21201, USA
9
Laboratory of Public Health, Faculty of Veterinary Medicine, Hokkaido University, N18 W9, Kita-ku, Sapporo 060-0818, Japan
*
Author to whom correspondence should be addressed.
Academic Editor: Concetta Castilletti
Viruses 2021, 13(3), 384; https://doi.org/10.3390/v13030384
Received: 5 February 2021 / Revised: 21 February 2021 / Accepted: 25 February 2021 / Published: 28 February 2021
(This article belongs to the Special Issue SARS-CoV-2 Host Cell Interactions)
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) utilizes host proteases, including a plasma membrane-associated transmembrane protease, serine 2 (TMPRSS2) to cleave and activate the virus spike protein to facilitate cellular entry. Although TMPRSS2 is a well-characterized type II transmembrane serine protease (TTSP), the role of other TTSPs on the replication of SARS-CoV-2 remains to be elucidated. Here, we have screened 12 TTSPs using human angiotensin-converting enzyme 2-expressing HEK293T (293T-ACE2) cells and Vero E6 cells and demonstrated that exogenous expression of TMPRSS11D and TMPRSS13 enhanced cellular uptake and subsequent replication of SARS-CoV-2. In addition, SARS-CoV-1 and SARS-CoV-2 share the same TTSPs in the viral entry process. Our study demonstrates the impact of host TTSPs on infection of SARS-CoV-2, which may have implications for cell and tissue tropism, for pathogenicity, and potentially for vaccine development.
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Keywords:
severe acute respiratory syndrome-like coronavirus-2 (SARS-CoV-2); type II transmembrane serine protease (TTSP); spike protein
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MDPI and ACS Style
Kishimoto, M.; Uemura, K.; Sanaki, T.; Sato, A.; Hall, W.W.; Kariwa, H.; Orba, Y.; Sawa, H.; Sasaki, M. TMPRSS11D and TMPRSS13 Activate the SARS-CoV-2 Spike Protein. Viruses 2021, 13, 384. https://doi.org/10.3390/v13030384
AMA Style
Kishimoto M, Uemura K, Sanaki T, Sato A, Hall WW, Kariwa H, Orba Y, Sawa H, Sasaki M. TMPRSS11D and TMPRSS13 Activate the SARS-CoV-2 Spike Protein. Viruses. 2021; 13(3):384. https://doi.org/10.3390/v13030384
Chicago/Turabian StyleKishimoto, Mai; Uemura, Kentaro; Sanaki, Takao; Sato, Akihiko; Hall, William W.; Kariwa, Hiroaki; Orba, Yasuko; Sawa, Hirofumi; Sasaki, Michihito. 2021. "TMPRSS11D and TMPRSS13 Activate the SARS-CoV-2 Spike Protein" Viruses 13, no. 3: 384. https://doi.org/10.3390/v13030384
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