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    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; 200(1) — S. 20–25
    ISSN: 0022-1899
    Sprache
    Englisch
    Verweise
    DOI: 10.1086/599316
    Pubmed: 19456260
    Kontakt
    Institut für Virologie

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    Gebäude 35
    14163 Berlin
    Tel. +49 30 838 51833 Fax. +49 30 838 451847
    email:viro@zedat.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.