A transmembrane serine protease is linked to the severe acute respiratory syndrome coronavirus receptor and activates virus entry

Ana Shulla; Taylor Heald-Sargent; Gitanjali Subramanya; Jincun Zhao; Stanley Perlman; Tom Gallagher

doi:10.1128/JVI.02062-10

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A transmembrane serine protease is linked to the severe acute respiratory syndrome coronavirus receptor and activates virus entry

Journal article

Open access

Peer reviewed

A transmembrane serine protease is linked to the severe acute respiratory syndrome coronavirus receptor and activates virus entry

Ana Shulla, Taylor Heald-Sargent, Gitanjali Subramanya, Jincun Zhao, Stanley Perlman and Tom Gallagher

Journal of virology, Vol.85(2), pp.873-882

01/2011

DOI: 10.1128/JVI.02062-10

PMCID: PMC3020023

PMID: 21068237

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https://europepmc.org/articles/pmc3020023View

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Abstract

Spike (S) proteins, the defining projections of the enveloped coronaviruses (CoVs), mediate cell entry by connecting viruses to plasma membrane receptors and by catalyzing subsequent virus-cell membrane fusions. The latter membrane fusion requires an S protein conformational flexibility that is facilitated by proteolytic cleavages. We hypothesized that the most relevant cellular proteases in this process are those closely linked to host cell receptors. The primary receptor for the human severe acute respiratory syndrome CoV (SARS) CoV is angiotensin-converting enzyme 2 (ACE2). ACE2 immunoprecipitation captured transmembrane protease/serine subfamily member 2 (TMPRSS2), a known human airway and alveolar protease. ACE2 and TMPRSS2 colocalized on cell surfaces and enhanced the cell entry of both SARS S-pseudotyped HIV and authentic SARS-CoV. Enhanced entry correlated with TMPRSS2-mediated proteolysis of both S and ACE2. These findings indicate that a cell surface complex comprising a primary receptor and a separate endoprotease operates as a portal for activation of SARS-CoV cell entry.

Cell Membrane - chemistry

Cell Line

Immunoprecipitation

Receptors, Virus - metabolism

Humans

Peptidyl-Dipeptidase A - metabolism

SARS Virus - physiology

Serine Endopeptidases - metabolism

Virus Internalization

Details

Title: Subtitle: A transmembrane serine protease is linked to the severe acute respiratory syndrome coronavirus receptor and activates virus entry
Creators: Ana Shulla - Department of Microbiology and Immunology, Loyola University Medical Center, 2160 South First Avenue, Maywood, IL 60153, USA
Taylor Heald-Sargent
Gitanjali Subramanya
Jincun Zhao
Stanley Perlman
Tom Gallagher
Resource Type: Journal article
Publication Details: Journal of virology, Vol.85(2), pp.873-882
DOI: 10.1128/JVI.02062-10
PMID: 21068237
PMCID: PMC3020023
NLM abbreviation: J Virol
ISSN: 0022-538X
eISSN: 1098-5514
Publisher: United States
Grant note: AI060030 / NIAID NIH HHS R01 AI060030 / NIAID NIH HHS R01 AI091322 / NIAID NIH HHS
Language: English
Date published: 01/2011
Academic Unit: Microbiology and Immunology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
Record Identifier: 9983777345102771

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