Genetic mapping of vector competence in Culicoides sonorensis

库蚊是50多种虫媒病毒(由节肢动物媒介传播的病毒)的媒介，包括具有国际、经济和动物福利重要性的一些最具经济破坏性的牲畜疾病。这些病毒包括蓝舌病毒(BTV)和非洲马病病毒(AHSV)。2006年，在荷兰发现了有记录以来北欧的第一例BTV病例。该病毒随后在欧洲的大片地区蔓延，导致了有记录以来代价最高的一次蓝舌病(Bt)疫情，损失高达数亿欧元。2007年8月，该疾病抵达英格兰东南部，2008年，只有快速的疫苗接种运动才阻止了它在英国再次出现。据估计，这为英国节省了4.85亿英镑。整个欧洲现在必须被视为处于Bt和包括非洲马病病毒(AHSV)在内的其他虫媒病毒疾病进一步爆发的“风险”之中。后者是马匹最可怕的病原体之一，在易感人群中的死亡率可达95%。已经知道，蚊虫基因的变异会影响它们感染BTV并随后感染动物宿主的能力(这被称为媒介能力)。这对BTV在全球的传播产生了重大影响，因为该病毒只能在有合格蚊子存在的情况下长期存活。我们的目标是发现是什么基因控制着这种载体能力。为了做到这一点，我们将首先使用在IAH举行的索诺尔库蚊群体生成完整的遗传图谱(基因组)。到目前为止，已经为三种蚊子制作了类似的基因组，并正在为采采蝇、沙蝇、黑蝇、家蝇和其他蚊媒物种进行额外的项目。尽管我们已经生成了初步测序数据，表明利用最近的技术进步可以相对快速地实现这一点，但尚未尝试对任何库蚊物种进行全基因组测序。一旦我们制作了蚊子的遗传图谱，我们就会检查和分类种群中个体蚊子之间的所有遗传差异。这些信息将使我们能够识别影响蚊子感染和传播病毒(特别是BTV和AHSV)能力的不同版本的基因。除了提供库蚊和这些病毒如何相互作用的知识外，我们的提议还将为这个昆虫媒介组生成第一个带注释的基因组。这将为研究这些重要的疾病媒介提供巨大的新机会。它还将使我们能够将索诺氏锥虫的基因与其他已有基因组序列的昆虫群体(如蚊子)进行比较。这项研究中产生的库蚊基因组序列也将为理解BTV和AHSV在分布上受到限制的原因以及为什么会发生BTV这样的入侵北欧提供一个长期的基本工具。

Culicoides midges act as vectors of more than 50 arboviruses (viruses transmitted by arthropods vectors), including some of the most economically damaging diseases of livestock that are of international, economic and animal-welfare importance. These include Bluetongue virus (BTV) and African horse sickness virus (AHSV). In 2006 the first cases of BTV in Northern Europe in recorded history were detected in the Netherlands. The virus subsequently spread across a vast area of Europe, causing the most costly single outbreak of bluetongue (BT) in recorded history, with losses running into hundreds of millions of Euro's. The disease arrived in South-East England during August 2007, and only a rapid vaccination campaign prevented its re-emergence in the UK during 2008. This is estimated to have saved the UK ~£485 million. The whole of Europe must now be regarded as 'at risk' from further outbreaks of BT and other arboviral diseases including African horse sickness virus (AHSV). The latter is one of the most feared pathogens of horses with mortality rates in susceptible populations that can reach 95%. It is already known that variation in midge genes influences their ability to become infected by BTV and to subsequently infect animal hosts (this is termed their vector competence). This has a major impact on the distribution of BTV worldwide, as the virus can only survive for long periods where competent midges are present. We aim to discover what genes control this vector competence. To do this we will first generate the complete genetic map (genome) for this group using colonies of Culicoides sonorensis held at IAH. To date, similar genomes have been produced for three mosquitoes with additional projects underway for the tsetse fly, the sandfly, the blackfly, the housefly and additional mosquito vector species. Full genome sequencing has not yet been attempted for any Culicoides species although we have generated preliminary sequencing data that shows that this can be achieved relatively rapidly with recent technological advances. Once we have produced the genetic map of the midge we will then examine and catalogue all genetic differences between the individual midges in the population. This information will allow us to identify different versions of genes that influence the ability of the midge to become infected and transmit viruses (specifically BTV and AHSV). In addition to providing knowledge of how Culicoides and these viruses interact, our proposal will also generate the first annotated genome for this insect vector group. This will provide vast new opportunities in research on these important disease vectors. It will also allow us to compare the genes from C. sonorensis with other insect groups (e.g. mosquitoes) for which genome sequences are already available. The genome sequence of Culicoides generated in this study will also provide a long term fundamental tool for understanding the reasons which both BTV and AHSV are restricted in distribution and also why incursions such as that of BTV into northern Europe occur.