title: The E glycoprotein plays an essential role in the high pathogenicity of European-Mediterranean IS98 strain of West Nile virus.
abstract: West Nile virus (WNV) is the most widespread arbovirus in the world. Several recent outbreaks and epizootics have been reported in Europe and the Mediterranean basin with increased virulence. In contrast to the well-characterized American and Australian strains, little is known about the virulence determinants of the WNV European-Mediterranean strains. To investigate the viral factors involved in the virulence of these strains, we generated chimeras between the highly neuropathogenic Israel 1998 (IS-98-ST1, IS98) strain and the non-pathogenic Malaysian Kunjin virus (KJMP-502). In vivo analyses in a mouse model of WNV pathogenesis shows that chimeric virus where KJMP-502 E glycoprotein was replaced by that of IS98 is neuropathogenic, demonstrating that this protein is a major virulence determinant. Presence of the N-glycosylation site had limited impact on virus virulence and the 5'UTR does not seem to influence pathogenesis. Finally, mice inoculated with KJMP-502 virus were protected against lethal IS98 infection.
authors.affiliation: Institut Pasteur, URE ERI/CIBU, Paris, France.
authors.forename: Khaled
authors.initials: K
authors.lastname: Alsaleh
authors.affiliation: Institut Pasteur, URE ERI/CIBU, Paris, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Khou
authors.affiliation: Institut Pasteur, URE ERI/CIBU, Paris, France.
authors.forename: Marie-Pascale
authors.initials: MP
authors.lastname: Frenkiel
authors.affiliation: French Agency for Food, Environmental and Occupational Health & Safety (ANSES), Animal Health Laboratory, UMR1161 Virology, INRA, ANSES, ENVA, Maisons-Alfort, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Lecollinet
authors.affiliation: Arbovirus & Imported Viral Diseases, Centro Nacional de Microbiología, Ctra. Pozuelo, Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Vàzquez
authors.affiliation: Arbovirus & Imported Viral Diseases, Centro Nacional de Microbiología, Ctra. Pozuelo, Madrid, Spain.
authors.forename: Eva Ramírez
authors.initials: ER
authors.lastname: de Arellano
authors.affiliation: University of La Réunion Island, UM134 PIMIT, INSERM U1187, CNRS UMR9192, IRD UMR249, Technology Platform CYROI, 97490 Saint-Clotilde, La Réunion, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Després
authors.affiliation: Institut Pasteur, URE ERI/CIBU, Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Pardigon
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D007114:Immunization; D019083:Mediterranean Region / Q000453:epidemiology; D051379:Mice; D008807:Mice, Inbred BALB C; D017434:Protein Structure, Tertiary; D016865:Reassortant Viruses / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D016019:Survival Analysis; D014613:Vaccines, Attenuated; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage*; D014901:West Nile Fever / Q000453:epidemiology / Q000276:immunology / Q000401:mortality / Q000517:prevention & control*; D014902:West Nile virus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*
chemical_list: D014613:Vaccines, Attenuated; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C065696:glycoprotein E, Flavivirus
keywords: Chimeric virus; Flavivirus; Infectious clones; Kunjin virus; Mouse; Pathogenesis; Virulence factors; West Nile virus