title: OAS1 polymorphisms are associated with susceptibility to West Nile encephalitis in horses.
abstract: West Nile virus, first identified within the United States in 1999, has since spread across the continental states and infected birds, humans and domestic animals, resulting in numerous deaths. Previous studies in mice identified the Oas1b gene, a member of the OAS/RNASEL innate immune system, as a determining factor for resistance to West Nile virus (WNV) infection. A recent case-control association study described mutations of human OAS1 associated with clinical susceptibility to WNV infection. Similar studies in horses, a particularly susceptible species, have been lacking, in part, because of the difficulty in collecting populations sufficiently homogenous in their infection and disease states. The equine OAS gene cluster most closely resembles the human cluster, with single copies of OAS1, OAS3 and OAS2 in the same orientation. With naturally occurring susceptible and resistant sub-populations to lethal West Nile encephalitis, we undertook a case-control association study to investigate whether, similar to humans (OAS1) and mice (Oas1b), equine OAS1 plays a role in resistance to severe WNV infection. We identified naturally occurring single nucleotide mutations in equine (Equus caballus) OAS1 and RNASEL genes and, using Fisher's Exact test, we provide evidence that mutations in equine OAS1 contribute to host susceptibility. Virtually all of the associated OAS1 polymorphisms were located within the interferon-inducible promoter, suggesting that differences in OAS1 gene expression may determine the host's ability to resist clinical manifestations associated with WNV infection.
authors.affiliation: McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Rios
authors.forename: Joann G W
authors.initials: JG
authors.lastname: Fleming
authors.forename: Uneeda K
authors.initials: UK
authors.lastname: Bryant
authors.forename: Craig N
authors.initials: CN
authors.lastname: Carter
authors.forename: John C
authors.initials: JC
authors.lastname: Huber
authors.forename: Maureen T
authors.initials: MT
authors.lastname: Long
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Spencer
authors.forename: David L
authors.initials: DL
authors.lastname: Adelson
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics*; D000483:Alleles; D000818:Animals; D016022:Case-Control Studies; D005347:Fibroblasts / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D056945:Hep G2 Cells; D006734:Horse Diseases / Q000201:enzymology* / Q000235:genetics / Q000821:virology*; D006736:Horses / Q000235:genetics* / Q000821:virology; D006801:Humans; D007372:Interferons / Q000494:pharmacology; D008156:Luciferases; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D014901:West Nile Fever / Q000201:enzymology / Q000235:genetics / Q000662:veterinary* / Q000821:virology
chemical_list: D007372:Interferons; D008156:Luciferases; D015088:2',5'-Oligoadenylate Synthetase