Genetic mapping of vector competence in Culicoides sonorensis

库蠓是50多种虫媒病毒（通过节肢动物媒介传播的病毒）的媒介，包括对国际、经济和动物福利具有重要意义的一些最具经济破坏性的牲畜疾病。其中包括蓝舌病病毒（BTV）和非洲马病病毒（AHSV）。2006年，在荷兰发现了北欧有记录以来的第一例BTV病例。这种病毒随后在欧洲大片地区蔓延，造成了有史以来代价最高的蓝舌病（BT）爆发，损失高达数亿欧元。该疾病于2007年8月抵达英格兰东南部，2008年期间，只有快速的疫苗接种运动才阻止了它在英国的再次出现。据估计，这为英国节省了约4.85亿英镑。现在必须将整个欧洲视为BT和其他虫媒病毒性疾病（包括非洲马病病毒（AHSV））进一步爆发的“危险”。后者是马最可怕的病原体之一，易感人群的死亡率可达95%。众所周知，蠓基因的变异会影响它们被BTV感染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，因为该病毒只能在存在有能力的蠓的地方存活很长时间。我们的目标是发现控制这种载体能力的基因。为此，我们将首先使用在IAH保存的sonorensis库蠓菌落生成该群体的完整遗传图谱（基因组）。迄今为止，已经对三种蚊子产生了类似的基因组，正在对采采蝇、白蛉、黑蝇、家蝇和其他蚊子媒介物种进行更多的项目。尽管我们已经产生了初步的测序数据，但尚未尝试对任何库蠓物种进行全基因组测序，这些数据表明，随着最近的技术进步，这可以相对较快地实现。一旦我们绘制出蠓的遗传图谱，我们就会对种群中单个蠓之间的所有遗传差异进行检查和编目。这些信息将使我们能够确定影响蠓感染和传播病毒（特别是BTV和AHSV）能力的不同版本的基因。除了提供库蠓和这些病毒如何相互作用的知识外，我们的提议还将为这种昆虫载体组生成第一个注释基因组。这将为研究这些重要的病媒提供巨大的新机会。它还将使我们能够将索诺索蚊的基因与已经获得基因组序列的其他昆虫类群（例如蚊子）的基因进行比较。本研究生成的库蠓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BTV入侵北欧的原因提供长期的基础工具。

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.