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

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 (Oas1bMBT) into BALB/c mice homozygous for the X253 allele (Oas1bBALB/c). Overexpression of Oas1bMBT 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 Oas1bMBT 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 Oas1bBALB/c mRNA was unable to prevent virally-induced encephalitis, confirming the critical role of the R253X mutation on Oas1b activity in live mice.