title: Susceptibility to SARS coronavirus S protein-driven infection correlates with expression of angiotensin converting enzyme 2 and infection can be blocked by soluble receptor.
abstract: The angiotensin converting enzyme 2 (ACE2) has been identified as a receptor for the severe acute respiratory syndrome associated coronavirus (SARS-CoV). Here we show that ACE2 expression on cell lines correlates with susceptibility to SARS-CoV S-driven infection, suggesting that ACE2 is a major receptor for SARS-CoV. The soluble ectodomain of ACE2 specifically abrogated S-mediated infection and might therefore be exploited for the generation of inhibitors. Deletion of a major portion of the cytoplasmic domain of ACE2 had no effect on S-driven infection, indicating that this domain is not important for receptor function. Our results point to a central role of ACE2 in SARS-CoV infection and suggest a minor contribution of the cytoplasmic domain to receptor function.
authors.affiliation: Chair of Genetics, University of Erlangen-Nürnberg, 91054 Erlangen, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Hofmann
authors.forename: Martina
authors.initials: M
authors.lastname: Geier
authors.forename: Andrea
authors.initials: A
authors.lastname: Marzi
authors.forename: Mandy
authors.initials: M
authors.lastname: Krumbiegel
authors.forename: Matthias
authors.initials: M
authors.lastname: Peipp
authors.forename: Georg H
authors.initials: GH
authors.lastname: Fey
authors.forename: Thomas
authors.initials: T
authors.lastname: Gramberg
authors.forename: Stefan
authors.initials: S
authors.lastname: Pöhlmann
mesh_terms: D000595:Amino Acid Sequence; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000378:metabolism*; D002268:Carboxypeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004198:Disease Susceptibility; D006801:Humans; D009154:Mutation; D007703:Peptidyl-Dipeptidase A; D017434:Protein Structure, Tertiary; D011991:Receptors, Virus / Q000378:metabolism*; D045473:Severe acute respiratory syndrome-related coronavirus / Q000378:metabolism* / Q000472:pathogenicity; D016415:Sequence Alignment; D045169:Severe Acute Respiratory Syndrome / Q000378:metabolism*; D012995:Solubility; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D000998:Antiviral Agents; D011991:Receptors, Virus; D014764:Viral Proteins; D002268:Carboxypeptidases; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2