Viruses
. 2021 Feb 28;13(3):384.
doi: 10.3390/v13030384.
TMPRSS11D and TMPRSS13 Activate the SARS-CoV-2 Spike Protein
Mai Kishimoto 1 , Kentaro Uemura 2 3 4 , Takao Sanaki 2 3 , Akihiko Sato 2 3 , William W Hall 5 6 7 8 , Hiroaki Kariwa 9 , Yasuko Orba 1 7 , Hirofumi Sawa 1 7 8 , Michihito Sasaki 1
Affiliations
- PMID: 33671076
- DOI: 10.3390/v13030384
Abstract
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.
Keywords: Severe acute respiratory syndrome-like coronavirus-2 (SARS-CoV-2); spike protein; type II transmembrane serine protease (TTSP).