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Base génétique de la compatibilité naturelle entre les virus de la dengue et leurs moustiques vecteurs – DENGVEC

Role of mosquito vectors in dengue emergence

Genetic basis of natural compatibility between dengue viruses and their mosquito vectors

Understanding emerging arboviral diseases

Emerging arboviral (arthropod-borne viral) diseases among which chikungunya, West Nile and Rift Valley fevers are only the most recent examples represent one of the most serious threats to global public health. Among them, dengue is presently the most prevalent emerging arboviral disease of humans worldwide, with no vaccine or efficient drug available. Multi-disciplinary research programs are necessary to understand the mechanisms of arboviral emergence in order to fight them and to predict them. The goal of the present project is to better understand the constraints related to the genetic diversity of mosquito vectors in the emergence and evolution of dengue viruses. Toward this aim, we characterized the genetic specificity of natural compatibility between dengue viruses and Aedes aegypti, the main mosquito vector of dengue worldwide.

We developed an innovative genetic mapping strategy to survey genotype-by-genotype (GxG) interactions using outbred mosquito families that were experimentally exposed to genetically distinct isolates of two dengue virus serotypes derived from human patients.

Genetic loci associated with vector competence indices were detected in multiple regions of the mosquito genome. Importantly, correlation between genotype and phenotype was virus isolate-specific at several of these loci, indicating GxG interactions. The relatively high percentage of phenotypic variation explained by the markers associated with GxG interactions (ranging from 7.8% to 16.5%) is consistent with large-effect host genetic factors.

Our data demonstrate that GxG interactions between dengue viruses and mosquito vectors can be assigned to physical regions of the mosquito genome, some of which have a large effect on the phenotype. This finding establishes the existence of tangible host genetic factors underlying specific interactions between invertebrates and their pathogens in a natural system. Fine mapping of the uncovered genetic loci will elucidate the molecular mechanisms of mosquito-virus specificity.

Fansiri T, Fontaine A, Diancourt L, Caro V, Thaisomboonsuk B, Richardson JH, Jarman RG, Ponlawat A & Lambrechts L (2013) Genetic mapping of specific interactions between Aedes aegypti mosquitoes and dengue viruses. PLoS Genetics 9(8): e1003621.

Lambrechts L, Quillery E, Noël V, Richardson JH, Jarman RG, Scott TW & Chevillon C (2013) Specificity of resistance to dengue virus isolates is associated with genotypes of the mosquito antiviral gene Dicer-2. Proceedings of the Royal Society B 280(1751): 20122437.

Lambrechts L, Fansiri T, Pongsiri A, Thaisomboonsuk B, Klungthong C, Richardson JH, Ponlawat A, Jarman RG & Scott TW (2012) Dengue-1 virus clade replacement in Thailand associated with enhanced mosquito transmission. Journal of Virology 86(3): 1853-1861.

Lambrechts L, Paaijmans KP, Fansiri T, Carrington LB, Kramer LD, Thomas MB & Scott TW (2011) Impact of daily temperature fluctuations on dengue virus transmission by Aedes aegypti. Proceedings of the National Academy of Sciences of the U S A 108(18): 7460-7465.

Lambrechts L (2011) Quantitative genetics of Aedes aegypti vector competence for dengue viruses: towards a new paradigm? Trends in Parasitology 27(3): 111-14.

Lambrechts L (2010) Dissecting the genetic architecture of host-pathogen specificity. PLoS Pathogens 6(8): e1001019.

Lambrechts L, Scott TW & Gubler DJ (2010) Consequences of the expanding global distribution of Aedes albopictus for dengue virus transmission. PLoS Neglected Tropical Diseases 4(5): e646.

Project coordinator

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

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