Publikationsdatenbank

A single-nucleotide polymorphism in a herpesvirus DNA polymerase is sufficient to cause lethal neurological disease (2009)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Van de Walle, Gerlinde R

Goupil, Ryan

Wishon, Cassandra

Damiani, Armando

Perkins, Gillian A

Osterrieder, Nikolaus

Quelle

The Journal of infectious diseases

Bandzählung: 200

Heftzählung: 1

Seiten: 20 – 25

ISSN: 0022-1899

Sprache

Englisch

Verweise

DOI: 10.1086/599316

Pubmed: 19456260

Kontakt

Institut für Virologie

Robert-von-Ostertag-Str. 7-13
14163 Berlin
+49 30 838 51833
virologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

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.