Genetic mapping of vector competence in Culicoides sonorensis

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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.