title: Endoproteolytic processing of the ebola virus envelope glycoprotein: cleavage is not required for function.
abstract: Proteolytic processing is required for the activation of numerous viral glycoproteins. Here we show that the envelope glycoprotein from the Zaire strain of Ebola virus (Ebo-GP) is proteolytically processed into two subunits, GP1 and GP2, that are likely covalently associated through a disulfide linkage. Murine leukemia virions pseudotyped with Ebo-GP contain almost exclusively processed glycoprotein, indicating that this is the mature form of Ebo-GP. Mutational analysis identified a dibasic motif, reminiscent of furin-like protease processing sites, as the Ebo-GP cleavage site. However, analysis of Ebo-GP processing in LoVo cells that lack the proprotein convertase furin demonstrated that furin is not required for processing of Ebo-GP. In sharp contrast to other viral systems, we found that an uncleaved mutant of Ebo-GP was able to mediate infection of various cell lines as efficiently as the wild-type, proteolytically cleaved glycoprotein, indicating that cleavage is not required for the activation of Ebo-GP despite the conservation of a dibasic cleavage site in all filoviral envelope glycoproteins.
authors.affiliation: Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6076, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Wool-Lewis
authors.forename: P
authors.initials: P
authors.lastname: Bates
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D002461:Cell Line, Transformed; D006224:Cricetinae; D029043:Ebolavirus / Q000235:genetics / Q000378:metabolism*; D010450:Endopeptidases / Q000378:metabolism; D000939:Epitopes; D045683:Furin; D006801:Humans; D051379:Mice; D016297:Mutagenesis, Site-Directed; D010084:Oxidation-Reduction; D011489:Protein Denaturation; D011499:Protein Processing, Post-Translational; D011817:Rabbits; D013381:Subtilisins; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000939:Epitopes; D014759:Viral Envelope Proteins; C113189:envelope glycoprotein, Ebola virus; D010450:Endopeptidases; D013381:Subtilisins; D045683:Furin