Deep sequencing analysis of tick-borne encephalitis virus from questing ticks at natural foci reveals similarities between quasispecies pools of the virus

Deep sequencing analysis of tick-borne encephalitis virus from questing ticks at natural foci reveals similarities between quasispecies pools of the virus
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DOI:
10.1099/jgv.0.000704
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发表时间:
2017-03-01
影响因子:
3.8
通讯作者:
Johansson, Magnus
Johansson, Magnus
中科院分区:
医学3区
文献类型:
--
作者:
Asghar, Naveed;Pettersson, John H. -O.;Johansson, Magnus

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每年,蜱传脑炎病毒(TBEV)在欧洲和亚洲造成10000至15000人严重的中枢神经系统感染。TBEV通过需要蜱媒介和脊椎动物宿主的地方流行循环维持在环境中,并且TBEV对脊椎动物和无脊椎动物环境的适应对于TBEV在自然界中的持久性是必不可少的。这种适应是由病毒的RNA依赖性RNA聚合酶的易错性促进的,该聚合酶产生称为准种的遗传上不同的病毒变体。TBEV呈现一个焦点性地理分布模式,每个焦点代表一个TBEV热点。在这里,我们测序和表征两个TBEV基因组,JP-296和JP-554,从questing蜱在TBEV焦点在瑞典中部的蓖麻硬蜱。系统发育分析显示,新测序的菌株和三个先前测序的斯堪的纳维亚菌株Toro-2003,Saringe-2009和Mandal-2009之间存在地理聚类,它们起源于同一祖先。在这5个斯堪的纳维亚TBEV毒株中,只有Mandal-2009在3'非编码区(NCR)内显示出大的缺失,类似于高毒力TBEV毒株Hypr。JP-296、JP-554和Mandal-2009的深度测序显示,与具有截短的3'NCR的Mandal-2009中的低多样性相比,具有完整3' NCR的JP-296和JP-554具有显著高的准种多样性。单核苷酸多态性分析表明,40%的单核苷酸多态性是共同的准种种群之间的JP-296和JP-554,表明一个假定的机制TBEV如何持续存在,并保持在其自然疫源地。
Every year, tick-borne encephalitis virus (TBEV) causes severe central nervous system infection in 10 000 to 15 000 people in Europe and Asia. TBEV is maintained in the environment by an enzootic cycle that requires a tick vector and a vertebrate host, and the adaptation of TBEV to vertebrate and invertebrate environments is essential for TBEV persistence in nature. This adaptation is facilitated by the error-prone nature of the virus's RNA-dependent RNA polymerase, which generates genetically distinct virus variants called quasispecies. TBEV shows a focal geographical distribution pattern where each focus represents a TBEV hotspot. Here, we sequenced and characterized two TBEV genomes, JP-296 and JP-554, from questing Ixodes ricinus ticks at a TBEV focus in central Sweden. Phylogenetic analysis showed geographical clustering among the newly sequenced strains and three previously sequenced Scandinavian strains, Toro-2003, Saringe-2009 and Mandal-2009, which originated from the same ancestor. Among these five Scandinavian TBEV strains, only Mandal-2009 showed a large deletion within the 3' non-coding region (NCR), similar to the highly virulent TBEV strain Hypr. Deep sequencing of JP-296, JP-554 and Mandal-2009 revealed significantly high quasispecies diversity for JP-296 and JP-554, with intact 3' NCRs, compared to the low diversity in Mandal-2009, with a truncated 3' NCR. Single-nucleotide polymorphism analysis showed that 40% of the single-nucleotide polymorphisms were common between quasispecies populations of JP-296 and JP-554, indicating a putative mechanism for how TBEV persists and is maintained within its natural foci.