Oas1b-dependent Immune Transcriptional Profiles of West Nile Virus Infection in the Collaborative Cross

• DOI: 10.1534/g3.117.041624
• Publication Date: 2019-03-14T23:36:02Z
• Authors: Richard Green; Courtney Wilkins; Sunil Thomas; Aimee Sekine; Duncan M Hendrick; Kathleen Voss; Renee C Ireton; Michael Mooney; Jennifer T Go; Gabrielle Choonoo; Sophia Jeng; Fernando Pardo-Ma...; Martin T Ferris; Shannon McWeeney; Michael Gale
• Keywords: Flavivirus

Abstract The oligoadenylate-synthetase (Oas) gene locus provides innate immune resistance to virus infection. In mouse models, variation in the Oas1b influences host susceptibility flavivirus However, impact of Oas on overall programming and global expression among tissues different genetic backgrounds has not been defined. We examined how acts spleen brain tissue limit West Nile (WNV) disease across a range backgrounds. laboratory founder strains Collaborative Cross (CC) (A/J, C57BL/6J, 129S1/SvImJ, NOD/ShiLtJ, NZO/HlLtJ) all encode truncated, defective Oas1b, whereas three wild-derived inbred (CAST/EiJ, PWK/PhJ, WSB/EiJ) full-length OAS1B protein. assessed profiles transcriptional signatures F1 hybrids derived from these strains. included wild-type (F/F), homozygous null (N/N), heterozygous offspring both parental combinations (F/N N/F). These mice were challenged with WNV, samples harvested for analysis. found that haplotype played role WNV metrics, but presence functional allele did absolutely predict protection against disease. Our results indicate status as or dosage, link novel specific biological pathways control infection immunity through Oas1b-dependent independent processes.