Enhanced polymerase activity confers replication competence of Borna disease virus in mice

Enhanced polymerase activity confers replication competence of Borna disease virus in mice
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DOI:
10.1099/vir.0.83170-0
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发表时间:
2007-11-01
影响因子:
3.8
通讯作者:
Staeheli, Peter
Staeheli, Peter
中科院分区:
医学3区
文献类型:
--
作者:
Ackermann, Andreas;Kugel, Daniela;Staeheli, Peter

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我们以前表明,小鼠适应cDNA衍生的博尔纳病病毒(BDV)株He/80(FR)的病毒聚合酶复合体中的突变完全相关。有趣的是,非重组He/80的独立小鼠适应与聚合酶的不同改变和病毒糖蛋白的突变相关。我们使用反向遗传学来证明,提高酶活性的聚合酶的变化代表了决定性的宿主范围突变。糖蛋白突变没有赋予小鼠复制能力,尽管如果与聚合酶突变结合,它们略微改善了病毒性能。我们的研究结果表明病毒聚合酶限制了BDV的宿主范围。
We previously showed that mouse adaptation of cDNA-derived Borna disease virus (BDV) strain He/80(FR) was associated exclusively with mutations in the viral polymerase complex. Interestingly, independent mouse adaptation of non-recombinant He/80 was correlated with different alterations in the polymerase and mutations in the viral glycoprotein. We used reverse genetics to demonstrate that changes in the polymerase which improve enzymatic activity represent the decisive host range mutations. The glycoprotein mutations did not confer replication competence in mice, although they slightly improved viral performance if combined with polymerase mutations. Our findings suggest that the viral polymerase restricts the host range of BDV.