Endoproteolytic processing of the ebola virus envelope glycoprotein: cleavage is not required for function.
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.
Wool-Lewis
R J
RJ
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6076, USA.
Bates
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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*
D000939:Epitopes; D014759:Viral Envelope Proteins; C113189:envelope glycoprotein, Ebola virus; D010450:Endopeptidases; D013381:Subtilisins; D045683:Furin