title: [Protease-dependent cell entry mechanism of coronaviruses].
abstract: Previous studies have demonstrated that the SARS-CoV S protein requires proteolytic cleavage by elastase, cathepsin or TMPRSS2 for S-mediated cell-cell or virus-cell membrane fusion. Activation of viral glycoprotein (GP) by protease also has been reported for influenza virus. The most distinctive difference between influenza virus and SARS-CoV is the stage during virus replication in which viral glycoproteins are cleaved by proteases. In influenza virus, the protease makes a simple cut in the GP during maturation. In contrast, SARS-CoV S protein is cleaved by the protease following receptor-induced conformational changes. The protease cleavage site in S protein is thought to be exposed only after receptor binding. In support of this model, we reported that the S protein of mouse hepatitis virus type 2 (MHV-2), which is highly similar to the S protein of SARS-CoV, requires two-step conformational changes mediated by sequential receptor binding and proteolysis to be activated for membrane fusion. Such a mechanism allows for tight temporal control over fusion by protecting the activating cleavage site from premature proteolysis yet allowing efficient cleavage upon binding to the receptor on target cells.
authors.affiliation: Dept. Virology III, National Institute of Infectious Diseases. matuyama@nih.go.jp
authors.forename: Shutoku
authors.initials: S
authors.lastname: Matsuyama
mesh_terms: D000818:Animals; D002403:Cathepsins / Q000502:physiology; D017934:Coronavirus / Q000472:pathogenicity*; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D006517:Murine hepatitis virus; D010196:Pancreatic Elastase / Q000502:physiology; D010447:Peptide Hydrolases / Q000502:physiology*; D012697:Serine Endopeptidases / Q000502:physiology; D045169:Severe Acute Respiratory Syndrome / Q000821:virology*; D064370:Spike Glycoprotein, Coronavirus; D014357:Trypsin / Q000502:physiology; D014759:Viral Envelope Proteins / Q000378:metabolism*; D056189:Viral Tropism; D053586:Virus Internalization
chemical_list: D008562:Membrane Glycoproteins; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins; C578557:spike glycoprotein, SARS-CoV; C578553:spike protein, mouse hepatitis virus; D002403:Cathepsins; D010447:Peptide Hydrolases; D012697:Serine Endopeptidases; C421305:TMPRSS2 protein, human; D010196:Pancreatic Elastase; D014357:Trypsin