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© Xavier Montagutelli, Institut Pasteur
Publication : Virology

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

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Virology - 17 Jun 2011

Simon-Chazottes D, Frenkiel MP, Montagutelli X, Guénet JL, Desprès P, Panthier JJ

Link to Pubmed [PMID] – 21683973

Virology 2011 Aug;417(1):147-53

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.