Virus and host factors affecting the clinical outcome of bluetongue virus infection.
Virus and host factors affecting the clinical outcome of bluetongue virus infection.
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DOI：
10.1128/jvi.01641-14
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发表时间：
2014-09
影响因子：
5.4
通讯作者：
Palmarini M
中科院分区：
文献类型：
--
作者：
Caporale M;Di Gialleonorado L;Janowicz A;Wilkie G;Shaw A;Savini G;Van Rijn PA;Mertens P;Di Ventura M;Palmarini M
蓝舌病是由蓝舌病病毒(BTV)引起的反刍动物的主要传染病，蓝舌病是一种由库蚊传播的虫媒病毒。在这里，我们使用一个单一的实验框架评估了影响BTV感染临床结局的病毒和宿主因素。我们调查了哺乳动物宿主物种、品种、年龄、BTV血清型和同一血清型中的菌株如何影响蓝舌病的临床病程。结果表明，在小型反刍动物中，对BTV引起的临床疾病的易感性在寄主物种水平上存在显著差异，而在品种水平上差异较小。不同的血清型(BTV-8和BTV-2)之间的毒力没有重大差异。然而，我们观察到在欧洲BTV-8暴发开始和结束时收集的相同血清型的密切相关毒株之间的毒力存在显著差异。正如之前观察到的，当动物感染BTV感染动物的血液或来自细胞培养中分离的相同病毒的血液时，也观察到疾病严重性的差异。有趣的是，除了两个沉默的突变外，全病毒基因组测序显示了细胞培养分离前后病毒相同的一致序列。然而，深度测序分析显示，在哺乳动物细胞中传代后，病毒群体的遗传多样性明显下降。相比之下，与从未在细胞培养中传代的病毒相比，在库蚊细胞中传代增加了低频变异的总数。因此，库蚊可能是新病毒变异的来源，而病毒种群多样性可能是影响BTV毒力的另一个因素。蓝舌病是反刍动物的主要传染病之一。它是由一种被称为蓝舌病毒(BTV)的虫媒病毒引起的。BTV感染的临床结果极不稳定。我们表明，蓝舌病的严重程度与感染的哺乳动物宿主物种之间存在明显的联系，而在品种水平上的差异不那么明显。两个不同的BTV血清型(BTV-8和BTV-2)的毒力没有差异。相反，我们发现2006年蓝舌病暴发初期分离的欧洲BTV-8毒株比暴发末期分离的毒株毒力更强。此外，我们发现BTV种群整体的变异性与毒力之间存在联系，我们的数据还表明，库蚊细胞可能是病毒变异的“孵化器”。
Bluetongue is a major infectious disease of ruminants caused by bluetongue virus (BTV), an arbovirus transmitted by Culicoides. Here, we assessed virus and host factors influencing the clinical outcome of BTV infection using a single experimental framework. We investigated how mammalian host species, breed, age, BTV serotypes, and strains within a serotype affect the clinical course of bluetongue. Results obtained indicate that in small ruminants, there is a marked difference in the susceptibility to clinical disease induced by BTV at the host species level but less so at the breed level. No major differences in virulence were found between divergent serotypes (BTV-8 and BTV-2). However, we observed striking differences in virulence between closely related strains of the same serotype collected toward the beginning and the end of the European BTV-8 outbreak. As observed previously, differences in disease severity were also observed when animals were infected with either blood from a BTV-infected animal or from the same virus isolated in cell culture. Interestingly, with the exception of two silent mutations, full viral genome sequencing showed identical consensus sequences of the virus before and after cell culture isolation. However, deep sequencing analysis revealed a marked decrease in the genetic diversity of the viral population after passaging in mammalian cells. In contrast, passaging in Culicoides cells increased the overall number of low-frequency variants compared to virus never passaged in cell culture. Thus, Culicoides might be a source of new viral variants, and viral population diversity can be another factor influencing BTV virulence. IMPORTANCE Bluetongue is one of the major infectious diseases of ruminants. It is caused by an arbovirus known as bluetongue virus (BTV). The clinical outcome of BTV infection is extremely variable. We show that there are clear links between the severity of bluetongue and the mammalian host species infected, while at the breed level differences were less evident. No differences were observed in the virulence of two different BTV serotypes (BTV-8 and BTV-2). In contrast, we show that the European BTV-8 strain isolated at the beginning of the bluetongue outbreak in 2006 was more virulent than a strain isolated toward the end of the outbreak. In addition, we show that there is a link between the variability of the BTV population as a whole and virulence, and our data also suggest that Culicoides cells might function as an “incubator” of viral variants.