Transgenic expression of full-length 2',5'-oligoadenylate synthetase 1b confers to BALB/c mice resistance against West Nile virus-induced encephalitis.

Dominique Simon-Chazottes (1) , Marie-Pascale Frenkiel (2) , Xavier Montagutelli (1) , Jean-Louis Guénet (3) , Philippe Desprès (2) , Jean-Jacques Panthier (1)

1 Génétique Fonctionnelle de la Souris
2 Interactions Moléculaires Flavivirus-Hôtes
3 Département de Biologie du Développement

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.

Mots clés: OAS; Transgenesis; Flavivirus; Mouse; Encephalitis; Inbred strains; Innate resistance; Genetic deficiency; Antiviral effect; Genetic determinant

Domaines: Génétique; Virologie

Dominique Simon-Chazottes, Marie-Pascale Frenkiel, Xavier Montagutelli, Jean-Louis Guénet, Philippe Desprès, et al.. Transgenic expression of full-length 2',5'-oligoadenylate synthetase 1b confers to BALB/c mice resistance against West Nile virus-induced encephalitis.. Virology, 2011, 417 (1), pp.147-53. ⟨10.1016/j.virol.2011.05.018⟩. ⟨pasteur-01325901⟩