title: RNA Editing of the GP Gene of Ebola Virus is an Important Pathogenicity Factor.
abstract: Synthesis of the surface glycoprotein GP of Ebola virus (EBOV) is dependent on transcriptional RNA editing, whereas direct expression of the GP gene results in synthesis of nonstructural secreted glycoprotein sGP. In this study, we investigate the role of RNA editing in the pathogenicity of EBOV using a guinea pig model and recombinant guinea pig-adapted EBOV containing mutations at the editing site, allowing expression of surface GP without the need for RNA editing, and also preventing synthesis of sGP. We demonstrate that the elimination of the editing site leads to EBOV attenuation in vivo, explained by lower virus spread caused by the higher virus cytotoxicity and, most likely, by an increased ability of the host defense systems to recognize and eliminate virus-infected cells. We also demonstrate that expression of sGP does not affect pathogenicity of EBOV in guinea pigs. In conclusion, data obtained indicate that downregulation of the level of surface GP expression through a mechanism of GP gene RNA editing plays an important role in the high pathogenicity of EBOV.
authors.affiliation: Molecular Basis of Viral Pathogenicity, CIRI, INSERM U1111 - CNRS UMR5308, Université de Lyon, Université Claude Bernard Lyon 1, France.
authors.forename: Valentina A
authors.initials: VA
authors.lastname: Volchkova
authors.affiliation: Molecular Basis of Viral Pathogenicity, CIRI, INSERM U1111 - CNRS UMR5308, Université de Lyon, Université Claude Bernard Lyon 1, France.
authors.forename: Olga
authors.initials: O
authors.lastname: Dolnik
authors.affiliation: Molecular Basis of Viral Pathogenicity, CIRI, INSERM U1111 - CNRS UMR5308, Université de Lyon, Université Claude Bernard Lyon 1, France.
authors.forename: Mikel J
authors.initials: MJ
authors.lastname: Martinez
authors.affiliation: Molecular Basis of Viral Pathogenicity, CIRI, INSERM U1111 - CNRS UMR5308, Université de Lyon, Université Claude Bernard Lyon 1, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Reynard
authors.affiliation: Molecular Basis of Viral Pathogenicity, CIRI, INSERM U1111 - CNRS UMR5308, Université de Lyon, Université Claude Bernard Lyon 1, France.
authors.forename: Viktor E
authors.initials: VE
authors.lastname: Volchkov
mesh_terms: D000818:Animals; D002460:Cell Line; D015536:Down-Regulation / Q000235:genetics; D029043:Ebolavirus / Q000235:genetics* / Q000472:pathogenicity; D015967:Gene Expression Regulation, Viral / Q000235:genetics; D005814:Genes, Viral / Q000235:genetics*; D006168:Guinea Pigs; D019142:Hemorrhagic Fever, Ebola / Q000821:virology*; D008562:Membrane Glycoproteins / Q000235:genetics; D009154:Mutation / Q000235:genetics; D017393:RNA Editing / Q000235:genetics*; D014759:Viral Envelope Proteins / Q000235:genetics*; D014764:Viral Proteins / Q000235:genetics*; D037521:Virulence Factors / Q000235:genetics*
chemical_list: D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins; D014764:Viral Proteins; D037521:Virulence Factors; C113189:envelope glycoprotein, Ebola virus
keywords: Ebola virus; RNA editing; editing site; glycoprotein GP; pathogenicity