Enhanced neurovirulence of Borna disease virus variants associated with nucleotide changes in the glycoprotein and L polymerase genes
Enhanced neurovirulence of Borna disease virus variants associated with nucleotide changes in the glycoprotein and L polymerase genes
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DOI：
10.1128/jvi.76.17.8650-8658.2002
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发表时间：
2002-09-01
影响因子：
5.4
通讯作者：
Carbone, KM
中科院分区：
文献类型：
--
作者：
Nishino, Y;Kobasa, D;Carbone, KM
博尔纳病病毒（BDV）感染产生多种临床疾病，从行为疾病到经典的致命性脑炎（即，Borna病[BD]）。由于大多数BDV分离株的基因组差异小于5%，因此宿主因素被认为是造成所报道的疾病表达变异性的主要原因。BDV基因组差异对BD表达变异的贡献在很大程度上未被探索。在这里，我们比较了感染两种相关BDV变体CRP 3或CRNP 5之一的大鼠的临床结果。与接种CRP 3的大鼠相比，接种CRP 5的成年和新生刘易斯大鼠具有更严重和快速致死的神经系统疾病，海马锥体神经元损伤增加，脑干神经元快速感染。为了确定可能的病毒特异性对观察到的疾病结果变异性的贡献，对CRP 3和CRNP 5的基因组进行了测序。与CRP 3相比，CRNP 5变体中有四个核苷酸变化，G蛋白和L聚合酶中各有两个，导致四个氨基酸变化。这些结果表明，BDV变体之间在G蛋白和/或L聚合酶中的少量基因组差异可导致BD结果的变异性。
Borna disease virus (BDV) infection produces a variety of clinical diseases, from behavioral illnesses to classical fatal encephalitis (i.e., Borna disease [BD]). Since the genomes of most BDV isolates differ by less than 5%, host factors are believed responsible for much of the reported variability in disease expression. The contribution of BDV genomic differences to variation in BD expression is largely unexplored. Here we compared the clinical outcomes of rats infected with one of two related BDV variants, CRP3 or CRNP5. Compared to rats inoculated with CRP3, adult and newborn Lewis rats inoculated with CRNP5 had more severe and rapidly fatal neurological disease, with increased damage to the hippocampal pyramidal neurons and rapid infection of brain stem neurons. To identify possible virus-specific contributions to the observed variability in disease outcome, the genomes of CRP3 and CRNP5 were sequenced. Compared to CRP3, there were four nucleotide changes in the CRNP5 variant, two each in the G protein and in the L polymerase, resulting in four amino acid changes. These results suggest that small numbers of genomic differences between BDV variants in the G protein and/or L polymerase can contribute to the variability in BD outcomes.