OAS1 polymorphisms are associated with susceptibility to West Nile encephalitis in horses

• Published in: PloS one 2010-05, Vol.5 (5), p.e10537-e10537
• Main Authors: Rios, Jonathan J, Fleming, Joann G W, Bryant, Uneeda K, Carter, Craig N, Huber, John C, Long, Maureen T, Spencer, Thomas E, Adelson, David L
• Format: Article
• Language: English
• Subjects: 2',5'-Oligoadenylate Synthetase - genetics; Alleles; Animal sciences; Animals; Ataxia; Biological response modifiers; Birds; Case-Control Studies; Clusters; Cytokines; Disease resistance; Disease susceptibility; Domestic animals; Encephalitis; Equus caballus; Fibroblasts; Fibroblasts - metabolism; Gene expression; Genes; Genetic aspects; Genetic polymorphisms; Genetic Predisposition to Disease; Genetics and Genomics/Animal Genetics; Genetics and Genomics/Disease Models; Genetics and Genomics/Genetics of Disease; Haplotypes - genetics; Health care; Hep G2 Cells; Hepatitis; Horse Diseases - enzymology; Horse Diseases - genetics; Horse Diseases - virology; Horses; Horses - genetics; Horses - virology; Humans; Immune system; Infections; Infectious Diseases/Infectious Diseases of the Nervous System; Infectious Diseases/Viral Infections; Innate immunity; Interferon; Interferons - pharmacology; Luciferases; Medical research; Mice; Mosquitoes; Mutation; Pichia pastoris; Polymorphism, Single Nucleotide - genetics; Population; Populations; Promoter Regions, Genetic - genetics; Proteins; Resistance factors; Studies; Vector-borne diseases; Veterinary medicine; Viral infections; Virology/Mechanisms of Resistance and Susceptibility, including Host Genetics; Viruses; West Nile fever; West Nile Fever - enzymology; West Nile Fever - genetics; West Nile Fever - veterinary; West Nile Fever - virology; West Nile virus; Zoology
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0010537

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.