A single-nucleotide polymorphism in a herpesvirus DNA polymerase is sufficient to cause lethal neurological disease.
A single-nucleotide polymorphism in a herpesvirus DNA polymerase is sufficient to cause lethal neurological disease.
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疱疹病毒 DNA 聚合酶中的单核苷酸多态性足以引起致命的神经系统疾病。
DOI：
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发表时间：
2009
影响因子：
6.4
通讯作者：
N. Osterrieder
中科院分区：
文献类型：
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作者：
G. R. Van de Walle;R. Goupil;Cassandra Wishon;A. Damiani;G. Perkins;N. Osterrieder
流行病学研究表明，马疱疹病毒1型DNA聚合酶基因的单核苷酸多态性与马高致死性神经系统疾病的爆发有关。反向遗传学实验进一步证明，在神经毒力株Ab4中引入G（2254）A（2254）核苷酸突变，导致天冬酰胺取代天冬氨酸（D（752）N（752）），使病毒在马中无神经毒力。在这里，我们报告了非神经毒性马疱疹病毒1型NY03株在A（2254）G（2254）（N（752）D（752））突变后引起马的致命神经系统疾病，从而提供了最终的证据，证明病毒DNA聚合酶中的D（752）等位基因对于在自然宿主中表达致命的神经毒性表型是必要的和足够的。虽然N（752）和D（752）变体之间的病毒脱落相当，但后者感染伴随着外周血单核细胞中有效建立的长期细胞相关病毒血症和6只动物中的2只神经系统疾病。
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.
喷昔洛韦和耐药单纯疱疹病毒突变体的发病机制表型。
影响因子：
7.6
作者：
Pelosi,E;Mulamba,GB;Coen,DM
通讯作者：
Coen,DM
影响因子：
2.7
作者：
Tischer, BK;von Einem, J;Osterrieder, N
通讯作者：
Osterrieder, N