TMPRSS11D and TMPRSS13 Activate the SARS-CoV-2 Spike Protein
Open Access
- 28 February 2021
- Vol. 13 (3), 384
- https://doi.org/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
Funding Information
- Japan Agency for Medical Research and Development (JP20wm0225003, JP20wm0125008, JP20fk0108104)
- Ministry of Education, Culture, Sports, Science and Technology (16H06429, 16H06431, 16K21723, 1801)
This publication has 40 references indexed in Scilit:
- Mechanisms of SARS-CoV-2 Transmission and PathogenesisTrends in Immunology, 2020
- High Prevalence of Concurrent Gastrointestinal Manifestations in Patients With Severe Acute Respiratory Syndrome Coronavirus 2: Early Experience From CaliforniaGastroenterology, 2020
- Potential of SARS-CoV-2 to Cause CNS Infection: Biologic Fundamental and Clinical ExperienceFrontiers in Neurology, 2020
- The involvement of the central nervous system in patients with COVID-19Progress in Neurobiology, 2020
- Evidence for Gastrointestinal Infection of SARS-CoV-2Gastroenterology, 2020
- Novel 2019 coronavirus structure, mechanism of action, antiviral drug promises and rule out against its treatmentJournal of Biomolecular Structure and Dynamics, 2020
- SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease InhibitorCell, 2020
- A new coronavirus associated with human respiratory disease in ChinaNature, 2020
- A pneumonia outbreak associated with a new coronavirus of probable bat originNature, 2020
- Enteric involvement of severe acute respiratory syndrome-associated coronavirus infectionGastroenterology, 2003