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Home / Equine Research Bank / J Infect Dis / A single-nucleotide polymorphism in a herpesvirus DNA polyme...
The Journal of infectious diseases2009; 200(1); 20-25; doi: 10.1086/599316

A single-nucleotide polymorphism in a herpesvirus DNA polymerase is sufficient to cause lethal neurological disease.

Abstract: Epidemiological studies have shown that a single-nucleotide polymorphism in the equid herpesvirus type 1 DNA polymerase gene is associated with outbreaks of highly lethal neurological disease in horses. Reverse genetics experiments further demonstrated that a G(2254) A(2254) nucleotide mutation introduced in neurovirulent strain Ab4, which resulted in an asparagine for aspartic acid substitution (D(752) N(752)), rendered the virus nonneurovirulent in the equine. Here, we report that the nonneurovirulent strain equid herpesvirus type 1 strain NY03 caused lethal neurological disease in horses after mutation of A(2254) G(2254) (N(752) D(752)), thereby providing final proof that the D(752) allele in the viral DNA polymerase is necessary and sufficient for expression of the lethal neurovirulent phenotype in the natural host. Although virus shedding was comparable between the N(752) and D(752) variants, infection with the latter was accompanied by efficient establishment of prolonged cell-associated viremia in peripheral blood mononuclear cells and neurological disease in 2 of 6 animals.
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Publication Date: 2009-05-22 PubMed ID: 19456260DOI: 10.1086/599316Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

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.

The research focuses on the impact of a single genetic mutation in a herpesvirus found in horses, determining that this one change can result in a lethal neurological disease.

Scientists Identified a Genetic Mutation Linked to Disease Outbreaks

  • The researchers began by noting that previous studies had identified a correlation between a single-nucleotide polymorphism (SNP) in the equid herpesvirus type 1 DNA polymerase gene and high-fatality neurological disease outbreaks among horses.
  • This SNP involves a change in the DNA sequence – specifically, a G(2254) A(2254) nucleotide mutation – in relation to a neurovirulent strain of the virus known as Ab4.
  • This mutation results in a substitution of an asparagine molecule for an aspartic acid molecule (D(752) N(752)), which in turn alters the behavior of the virus, making it nonneurovirulent or incapable of causing nerve-related diseases.

Research Experiment: Mutating a Nonneurovirulent Strain

  • In their experiment, the researchers introduced the A(2254) G(2254) mutation (which involves replacing an asparagine molecule with an aspartic acid molecule – N(752) D(752)) into a nonneurovirulent strain of the equid herpesvirus type 1 known as NY03.
  • After introducing this mutation, they found that the once nonneurovirulent NY03 strain became capable of causing lethal neurological diseases in horses.
  • This provided definitive evidence that the presence of the D(752) allele in the virus’s DNA polymerase gene is necessary and sufficient to produce a lethal, nerve-damaging variant of the virus.

Comparing Infections: N(752) vs D(752) Variants

  • Equid herpesvirus type 1 variants with either the N(752) or the D(752) allele were found to result in comparable levels of virus shedding, or the process through which the virus replicates and is expelled from a cell.
  • However, infections caused by the D(752) variant were associated with more prolonged viremia – the presence of the virus in the bloodstream – within peripheral blood mononuclear cells.
  • Moreover, 2 out of 6 horses infected with the D(752) variant developed neurological diseases, confirming the mutation’s neurovirulent capabilities.

Cite This Article

APA
Van de Walle GR, Goupil R, Wishon C, Damiani A, Perkins GA, Osterrieder N. (2009). A single-nucleotide polymorphism in a herpesvirus DNA polymerase is sufficient to cause lethal neurological disease. J Infect Dis, 200(1), 20-25. https://doi.org/10.1086/599316

Publication

The Journal of infectious diseases
ISSN: 0022-1899
NlmUniqueID: 0413675
Country: United States
Language: English
Volume: 200
Issue: 1
Pages: 20-25

Researcher Affiliations

Van de Walle, Gerlinde R
  • Department of Microbiology, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA
Goupil, Ryan
    Wishon, Cassandra
      Damiani, Armando
        Perkins, Gillian A
          Osterrieder, Nikolaus

            MeSH Terms

            • Animals
            • Antiviral Agents / therapeutic use
            • Aphidicolin / therapeutic use
            • DNA, Viral / blood
            • DNA, Viral / genetics
            • DNA-Directed DNA Polymerase / genetics
            • Genetic Variation
            • Herpesviridae Infections / drug therapy
            • Herpesviridae Infections / mortality
            • Herpesvirus 1, Equid / genetics
            • Herpesvirus 1, Equid / pathogenicity
            • Horse Diseases / mortality
            • Horse Diseases / virology
            • Horses
            • Microbial Sensitivity Tests
            • Polymorphism, Single Nucleotide
            • Virus Shedding

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