TMPRSS11D and TMPRSS13 Activate the SARS-CoV-2 Spike Protein

• Published in: Viruses Vol. 13; no. 3; p. 384
• Main Authors: Kishimoto, Mai, Uemura, Kentaro, Sanaki, Takao, Sato, Akihiko, Hall, William W., Kariwa, Hiroaki, Orba, Yasuko, Sawa, Hirofumi, Sasaki, Michihito
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 28.02.2021; MDPI
• Subjects: ACE2; Angiotensin; Angiotensin-converting enzyme 2; Angiotensin-Converting Enzyme 2 - metabolism; Animals; Antibodies; Chlorocebus aethiops; Cloning; Communication; Coronaviruses; COVID-19; COVID-19 - metabolism; COVID-19 - virology; Disease transmission; Efficiency; Enzymes; Genes; HEK293 Cells; Humans; Infections; Membrane Proteins - metabolism; Membranes; Pathogenicity; Peptidyl-dipeptidase A; Plasmids; Proteins; Replication; SARS-CoV-2 - metabolism; Serine; Serine Endopeptidases - metabolism; Serine Proteases - metabolism; Serine proteinase; serine proteinases; Severe acute respiratory syndrome coronavirus; Severe acute respiratory syndrome coronavirus 2; severe acute respiratory syndrome-like coronavirus-2 (SARS-CoV-2); Spike Glycoprotein, Coronavirus - metabolism; Spike protein; tissue tropism; Tropism; type II transmembrane serine protease (TTSP); Vaccine development; Vero Cells; Virus Internalization; Viruses; United States > US; Japan; Severe acute respiratory syndrome-like coronavirus-2 (SARS-CoV-2); type II transmembrane serine protease (TTSP); spike protein
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v13030384

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.