FP6Individual fellowship2007–2009

DENGUE VECTORS · Local adaptation and genetic interactions between dengue viruses and their mosquito vectors

FP6 — Marie Curie Actions (Human Resources and Mobility)

Duration
2007-01-01 → 2009-12-31
EU contribution
€242,287
Participants
2
Scheme
OIF

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Results in brief

Final Activity Report Summary - DENGUE VECTORS (Local adaptation and genetic interactions between dengue viruses and their mosquito vectors)

The specific compatibility between the genotypes of pathogens and their vectors has important implications for the incidence and evolution of vector-borne diseases. Earlier genetic studies on the interactions between aedes aegypti mosquitoes and dengue viruses (DENV) had most often used laboratory-tractable systems consisting of selected mosquito lines and a reference viral strain. Hence, the overall objective of this project was to test their validity by characterising the genetic specificity of mosquito-virus interactions in a natural system where both vector and viral populations were genetically diverse. We firstly measured the specificity of interactions between aedes aegypti and DENV by experimentally challenging several mosquito families which were derived from field-collected individuals with different, contemporaneous wild-type isolates of DENV-1. Most indices of vector competence, i.e. of the ability of an insect to be infected and subsequently transmit a pathogen, were strongly dependent on the specific combination of mosquito families and viral isolates, thus demonstrating significant specificity of genetic compatibility. We subsequently explored the molecular basis of this specificity by examining polymorphisms in key genes of the aedes aegypti ribonucleic acid interference (RNAi) pathway, which formed a major antiviral defence mechanism in mosquitoes. Variation in one gene (Dicer-2) was associated with isolate-specific infection phenotype, suggesting a possible role of this gene in vector-virus specific compatibility. In addition, we identified several genetic polymorphisms in the viral genomes that could be involved in specific interactions with mosquito vectors. The evidence for genetic specificity of interactions between DENV and aedes aegypti challenged the general relevance of conclusions from laboratory systems which were formed by a single combination of mosquito and DENV strains. Deciphering the molecular basis of specific compatibility between vector and pathogen strains was crucial for developing innovative vector control strategies which aimed to render wild mosquitoes resistant to all possible pathogen strains and predict the epidemic potential of a given virus when introduced into a novel vector population.

Data: CORDIS, © European Union

Project objective

Dengue is an emerging viral disease transmitted by mosquitoes that has become a major threat for public health in the tropics in the last 20 years. The mechanisms regulating dengue morbidity and epidemics remain to be elucidated, and disregarding the population biology of dengue viruses may have been a limiting factor.In particular, vector-driven selection is likely to play a key role on the evolution of viral populations, especially at a local geographical scale. A better understanding of dengue evolutionary and epidemiological dynamics thus requires a complete documentation on vector-virus interactions in natural populations.This proposal merges medical entomology, epidemiology, evolutionary biology, population genetics and virology to address the role o f vector-virus interactions in dengue transmission at local and regional scales.It aims at characterizing the interaction between dengue viruses and Aedesaegypti, the main dengue vector worldwide, by investigating- the occurrence of local adaptation o f dengue viruses to their mosquito vectors;- the association of mosquito polymorphism at potential vector competence genes with viral infection success, geography and viral genetic identity.The amount of viral adaptation to local vectors will be measured using a reciprocal cross-infection experiment of several combinations of mosquito and virus samples collected at different localities in Thailand (in collaboration with the joint Thai-US Army Laboratory in Bangkok).Sample collection and experimental infections will be conducted during a 20-month 'outgoing' phase at the University of California (USA), where the fellow will be trained in standard level-3 virological techniques.Mosquitoes and viruses involved in these experimental infections will then be processed for the genetic characterization of the interaction during a 16-month 'return' phase in Montpellier (France), allowing the fellow to acquire additional competencies in population genetics.

Original text from CORDIS.

Participants

  • CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE - DELEGATION LANGUEDOC-ROUSSILLON · MONTPELLIERCoordinatorCity levelFrance
  • UNIVERSITY OF CALIFORNIA AT DAVIS DEPARTMENT OF ENTOMOLOGY · DAVIS, CACountry levelUnited States

Links

Data: CORDIS, © European Union