title: Transgenic expression of full-length 2',5'-oligoadenylate synthetase 1b confers to BALB/c mice resistance against West Nile virus-induced encephalitis.
abstract: Susceptibility of inbred strains to infection with West Nile virus (WNV) has been genetically associated with an arginine-to-a nonsense codon substitution at position 253 (R253X) in the predicted sequence of the murine 2',5'-oligoadenylate synthetase 1B (OAS1B) protein. We introduced by transgenesis the Oas1b cDNA from MBT/Pas mice carrying the R253 codon (Oas1b(MBT)) into BALB/c mice homozygous for the X253 allele (Oas1b(BALB/c)). Overexpression of Oas1b(MBT) mRNA in the brain of transgenic mice prior and in the time course of infection provided protection against the neuroinvasive WNV strain IS-98-ST1. A 200-fold induction of Oas1b(MBT) mRNA in the brain of congenic BALB/c mice homozygous for a MBT/Pas segment encompassing the Oas1b gene was also efficient in reducing both viral growth and mortality, whereas a 200-fold induction of Oas1b(BALB/c) mRNA was unable to prevent virally-induced encephalitis, confirming the critical role of the R253X mutation on Oas1b activity in live mice.
authors.affiliation: Mouse Functional Genetics, Institut Pasteur, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Simon-Chazottes
authors.forename: Marie-Pascale
authors.initials: MP
authors.lastname: Frenkiel
authors.forename: Xavier
authors.initials: X
authors.lastname: Montagutelli
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Guénet
authors.forename: Philippe
authors.initials: P
authors.lastname: Desprès
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Panthier
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D015971:Gene Expression Regulation, Enzymologic; D005818:Genetic Engineering; D020022:Genetic Predisposition to Disease; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014901:West Nile Fever / Q000235:genetics* / Q000276:immunology / Q000821:virology; D014902:West Nile virus / Q000502:physiology*
chemical_list: D012333:RNA, Messenger; C509914:Oas1b protein, mouse; D015088:2',5'-Oligoadenylate Synthetase