School of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ, UK.
Bioinformatics. 2017 Jul 1;33(13):1911-1915. doi: 10.1093/bioinformatics/btx065.
Ebola viruses are not pathogenic but can be adapted to replicate and cause disease in rodents. Here, we used a structural bioinformatics approach to analyze the mutations associated with Ebola virus adaptation to rodents to elucidate the determinants of host-specific Ebola virus pathogenicity.
We identified 33 different mutations associated with Ebola virus adaptation to rodents in the proteins GP, NP, L, VP24 and VP35. Only VP24, GP and NP were consistently found mutated in rodent-adapted Ebola virus strains. Fewer than five mutations in these genes seem to be required for the adaptation of Ebola viruses to a new species. The role of mutations in GP and NP is not clear. However, three VP24 mutations located in the protein interface with karyopherin α5 may enable VP24 to inhibit karyopherins and subsequently the host interferon response. Three further VP24 mutations change hydrogen bonding or cause conformational changes. Hence, there is evidence that few mutations including crucial mutations in VP24 enable Ebola virus adaptation to new hosts. Since Reston virus, the only non-human pathogenic Ebolavirus species circulates in pigs in Asia, this raises concerns that few mutations may result in novel human pathogenic Ebolaviruses.
m.n.wass@kent.ac.uk , m.michaelis@kent.ac.uk or j.s.rossman@kent.ac.uk.
Supplementary data are available at Bioinformatics online.
埃博拉病毒本身并无致病性，但可以适应在啮齿动物中复制并引起疾病。在此，我们采用结构生物信息学方法分析与埃博拉病毒适应啮齿动物相关的突变，以阐明宿主特异性埃博拉病毒致病性的决定因素。
我们在 GP、NP、L、VP24 和 VP35 蛋白中鉴定出与埃博拉病毒适应啮齿动物相关的 33 种不同突变。只有 VP24、GP 和 NP 被一致发现存在于适应啮齿动物的埃博拉病毒株中发生突变。这些基因中少于五个的突变似乎足以使埃博拉病毒适应新物种。在 GP 和 NP 中突变的作用尚不清楚。然而，位于核孔蛋白 α5 蛋白界面的 VP24 中的三个突变可能使 VP24 能够抑制核孔蛋白，进而抑制宿主干扰素反应。另外三个 VP24 突变改变氢键或引起构象变化。因此，有证据表明，少数突变包括 VP24 中的关键突变，使埃博拉病毒能够适应新宿主。由于雷斯顿病毒是唯一在亚洲猪中循环的非人类致病性埃博拉病毒种，这引发了人们的担忧，即少数突变可能导致新型人类致病性埃博拉病毒的出现。
m.n.wass@kent.ac.uk、m.michaelis@kent.ac.uk 或 j.s.rossman@kent.ac.uk。
补充数据可在“Bioinformatics”在线获取。
