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PloS one2010; 5(5); e10537; doi: 10.1371/journal.pone.0010537

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.
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Publication Date: 2010-05-07 PubMed ID: 20479874PubMed Central: PMC2866329DOI: 10.1371/journal.pone.0010537Google Scholar: Lookup
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  • Journal Article
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research paper investigates if specific genetic variations in horses are linked to their susceptibility to West Nile encephalitis, a disease caused by the West Nile virus. The study finds that variations in the equine OAS1 gene, part of the horse’s innate immune system, increases their risk of severe West Nile Virus infection.

Background and Objective

  • The study is based on prior work which established that the Oas1b gene in mice plays a crucial role in resisting West Nile virus infection. Similarly, mutations in the human OAS1 gene have been associated with increased vulnerability to this virus.
  • Given these findings, the researchers aimed to examine if variations in the equine OAS1 gene had similar impacts on horses, a species known to be especially susceptible to West Nile virus.

Methodology

  • The research team conducted a case-control association study using horses that had naturally occurring sub-populations susceptible and resistant to the deadly West Nile encephalitis.
  • The study identified naturally occurring single nucleotide mutations in the equine (Equus caballus) OAS1 gene and another gene, RNASEL.
  • The team then used Fisher’s Exact Test to examine if the identified mutations in the equine OAS1 gene were related to host vulnerability.

Research Findings

  • The study found that mutations in the equine OAS1 does play a role in determining a horse’s resilience to severe WNV infection.
  • Almost all of the associated OAS1 polymorphisms were found within the interferon-inducible promoter, suggesting that OAS1 gene expression levels may play a significant role in resisting symptoms associated with WNV infection.

Implications

  • These findings provide valuable insights into the genetic factors contributing to the severity of West Nile Virus infection in horses, highlighting the importance of the OAS1 gene.
  • The results can pave the way for further research to understand and potentially manipulate the horse’s immune response to West Nile virus to improve clinical outcomes.

Cite This Article

APA
Rios JJ, Fleming JG, Bryant UK, Carter CN, Huber JC, Long MT, Spencer TE, Adelson DL. (2010). OAS1 polymorphisms are associated with susceptibility to West Nile encephalitis in horses. PLoS One, 5(5), e10537. https://doi.org/10.1371/journal.pone.0010537

Publication

PloS one
ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 5
Issue: 5
Pages: e10537
PII: e10537

Researcher Affiliations

Rios, Jonathan J
  • McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
Fleming, Joann G W
    Bryant, Uneeda K
      Carter, Craig N
        Huber, John C
          Long, Maureen T
            Spencer, Thomas E
              Adelson, David L

                MeSH Terms

                • 2',5'-Oligoadenylate Synthetase / genetics
                • Alleles
                • Animals
                • Case-Control Studies
                • Fibroblasts / metabolism
                • Genetic Predisposition to Disease
                • Haplotypes / genetics
                • Hep G2 Cells
                • Horse Diseases / enzymology
                • Horse Diseases / genetics
                • Horse Diseases / virology
                • Horses / genetics
                • Horses / virology
                • Humans
                • Interferons / pharmacology
                • Luciferases
                • Polymorphism, Single Nucleotide / genetics
                • Promoter Regions, Genetic / genetics
                • West Nile Fever / enzymology
                • West Nile Fever / genetics
                • West Nile Fever / veterinary
                • West Nile Fever / virology

                Conflict of Interest Statement

                The authors have declared that no competing interests exist.

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