Community Research and Development Information Service - CORDIS



Project ID: 281668
Funded under: FP7-IDEAS-ERC
Country: United Kingdom

Final Report Summary - DROSOPHILAINFECTION (Genetic variation in the susceptibility of Drosophila to infection)

Insect vectored viruses — arboviruses — are of considerable medical and economic importance. In humans there are 50-100 million new cases of dengue fever every year, and some of the most important emerging infectious diseases are arboviruses. For example, in Kenya there was an outbreak of Chikungunya virus in 2004 which spread throughout the Indian Ocean region causing millions of cases, including an outbreak in Italy. More recently, a major Zika virus epidemic has occurred. In agriculture, insects transmit numerous animal and plant viruses, resulting in substantial economic losses. These include arboviruses such as bluetongue and African horse sickness that are likely to become an increasing problem in Europe as a result of climate change. Viruses also have a direct impact on populations of economically important insects, and are thought to be important in the recent decline of honeybees. There is considerable genetic variation within and between species of insects in susceptibility to viral infection. For example, within populations of mosquitoes only certain genotypes efficiently transmit dengue fever. At the between-species level the differences are even greater, which can result in viruses being restricted to a limited range of host species. Drosophila is a model organism that is commonly used to investigate immune response of insects, and we have found similar variation in its susceptibility viruses. This project investigated the genetic causes of variation in susceptibility to viral infection in Drosophila.
Across multiple viruses we have repeatedly found that much of the variation in susceptibility to infection within populations is caused by polymorphisms that have large phenotypic effects. This contrasts with many other traits where many genes of small effect underlie natural variation. The existence of this variation is at first sight surprising, as one might expect that natural selection would eliminate the susceptible form of these genes. For one virus viruses we found that the resistant genes had recently arisen by mutation, and were spreading through populations. Therefore, the variation is a transient state, and is likely maintained over the long term as hosts must continually evolve new forms of resistance against an ever-changing pathogen community. The exception to this pattern was the polymorphism in a gene called Pastrel that had been maintained over long periods of time. To understand this process more, we turned to a different parasite, parasitoid wasps. Here we demonstrated that changes to the immune system in resistant flies were to the flies. These costs likely provide an advantage to susceptible flies in certain circumstances, and can maintain genetic variation within populations.
We identified several genes that control virus resistance, and confirmed the precise mutation involved by modifying these genes in transgenic flies, and this has implicated unexpected processes in virus resistance. Transposable elements are sections of DNA that copy themselves around the genome. We found that one of these elements had inserted into a gene in the fly genome. This resulted in a new gene that was a chimera between the transposable element and the original gene, and this made the flies highly resistant to the sigma virus. Remarkably, another insertion of the same transposable element in the coding sequence of a different gene confers almost total resistance to an unrelated virus called DAV. These results suggest an unexpected role of transposable elements in the evolution of virus resistance. We have identified other genes that confer resistance to viruses, and these have in turn implicated several other processes in antiviral defence. In the two genes that we studied in the most detail, we found that there were multiple forms of these genes within populations that provided differing levels of resistance to infection.

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United Kingdom
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