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

Viruses. 2021 Feb 28;13(3):384. 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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme 2 / metabolism
  • Animals
  • COVID-19 / metabolism*
  • COVID-19 / virology*
  • Chlorocebus aethiops
  • HEK293 Cells
  • Humans
  • Membrane Proteins / metabolism*
  • SARS-CoV-2 / metabolism*
  • Serine Endopeptidases / metabolism*
  • Serine Proteases / metabolism*
  • Spike Glycoprotein, Coronavirus / metabolism*
  • Vero Cells
  • Virus Internalization

Substances

  • Membrane Proteins
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Serine Proteases
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • Serine Endopeptidases
  • TMPRSS11D protein, human
  • TMPRSS13 protein, human
  • TMPRSS2 protein, human