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

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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.
Keywords
VIRUS, EQUINE HERPESVIRUS-1, MUTATION, MUTANTS, MICE

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MLA
Van de Walle, Gerlinde et al. “A Single-nucleotide Polymorphism in a Herpesvirus DNA Polymerase Is Sufficient to Cause Lethal Neurological Disease.” JOURNAL OF INFECTIOUS DISEASES 200.1 (2009): 20–25. Print.
APA
Van de Walle, G., Goupil, R., Wishon, C., Damiani, A., Perkins, G. A., & Osterrieder, N. (2009). A single-nucleotide polymorphism in a herpesvirus DNA polymerase is sufficient to cause lethal neurological disease. JOURNAL OF INFECTIOUS DISEASES, 200(1), 20–25. Presented at the 2nd Havemeyer Workshop on Equine Herpesvirus Type 1.
Chicago author-date
Van de Walle, Gerlinde, Ryan Goupil, Cassandra Wishon, Armando Damiani, Gillian A Perkins, and Nikolaus Osterrieder. 2009. “A Single-nucleotide Polymorphism in a Herpesvirus DNA Polymerase Is Sufficient to Cause Lethal Neurological Disease.” Journal of Infectious Diseases 200 (1): 20–25.
Chicago author-date (all authors)
Van de Walle, Gerlinde, Ryan Goupil, Cassandra Wishon, Armando Damiani, Gillian A Perkins, and Nikolaus Osterrieder. 2009. “A Single-nucleotide Polymorphism in a Herpesvirus DNA Polymerase Is Sufficient to Cause Lethal Neurological Disease.” Journal of Infectious Diseases 200 (1): 20–25.
Vancouver
1.
Van de Walle G, Goupil R, Wishon C, Damiani A, Perkins GA, Osterrieder N. A single-nucleotide polymorphism in a herpesvirus DNA polymerase is sufficient to cause lethal neurological disease. JOURNAL OF INFECTIOUS DISEASES. 2009;200(1):20–5.
IEEE
[1]
G. Van de Walle, R. Goupil, C. Wishon, A. Damiani, G. A. Perkins, and N. Osterrieder, “A single-nucleotide polymorphism in a herpesvirus DNA polymerase is sufficient to cause lethal neurological disease,” JOURNAL OF INFECTIOUS DISEASES, vol. 200, no. 1, pp. 20–25, 2009.
@article{933928,
  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.},
  author       = {Van de Walle, Gerlinde and Goupil, Ryan and Wishon, Cassandra and Damiani, Armando and Perkins, Gillian A and Osterrieder, Nikolaus},
  issn         = {0022-1899},
  journal      = {JOURNAL OF INFECTIOUS DISEASES},
  keywords     = {VIRUS,EQUINE HERPESVIRUS-1,MUTATION,MUTANTS,MICE},
  language     = {eng},
  location     = {Steamboat Springs, CO, USA},
  number       = {1},
  pages        = {20--25},
  title        = {A single-nucleotide polymorphism in a herpesvirus DNA polymerase is sufficient to cause lethal neurological disease},
  url          = {http://dx.doi.org/10.1086/599316},
  volume       = {200},
  year         = {2009},
}

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