DenWolution

Most prevalent arthropod-borne viral disease in tropical and subtropical countries, dengue remains a major public health concern worldwide. Dengue virus (DENV) is transmitted to humans by the bite of Aedes spp. mosquitoes, and can cause disease with a wide range of severities, from inapparent infection to classical dengue fever and severe, potentially fatal, forms of dengue. There are no specific antiviral therapeutics for dengue to date and the potential efficiency of a recently licensed vaccine remains uncertain. Current vector control measures regularly fail to prevent and control the emergence of epidemics. There is an urgent need to guide new vector control tools in order to determine the most effective interventions. Dengue is caused by one of four serotypes (DENV-1 to -4). DENV circulation and evolution are characterized by extensive genetic diversity and rapid turnover of DENV genotypes or lineages, including genotype replacements within the same serotype, leading to changes in dengue epidemiology or severity. However, the factors driving DENV evolution are still poorly understood. One promising strategy aiming at blocking DENV transmission involves the release of Aedes aegypti mosquitoes colonized by the endosymbiotic bacterium Wolbachia. This strategy is currently deployed in 12 countries including Noumea, New Caledonia (NC) by the World Mosquito Program (WMP). However, although promising results, this method might have limitations in the future. Indeed the impact of Wolbachia deployment on DENV evolution is unknown. In DenWOlution, we will take advantage of the release of wMel-infected Ae. aegypti in Noumea to investigate the reciprocal impact of the Wolbachia strategy and DENV evolution prior, during and after the intervention. NC represents an ideal setting to study the dynamics underlying DENV transmission and evolution under environmental constraints because: Ae. aegypti is the main vector for arboviruses, an effective arbovirus and entomological surveillance network has been in place for decades; DENV epidemiology is currently evolving from epidemic to endemic. In our project, we hypothesize that wMel-infected Ae. aegypti will shape both the evolution and the epidemiological dynamics of DENV in NC, and that DENV evolution upon environmental changes (Wolbachia-driven selective pressure) will ultimately impair the efficiency of the Wolbachia strategy. Thus, we intend to: i) Determine if DENV previous evolution in NC was stochastic or deterministic and how it impacted DENV epidemiological pattern; ii) Determine the reciprocal impact between DENV evolution and the Wolbachia strategy and iii) Model the impact of Wolbachia on DENV epidemiological profile in the upcoming years in the specific context of NC. Based on the analysis of over 250 DENV samples, the novelty of the DenWOlution project relies on its extensive spatio-temporal characterization of DENV evolution. This will allow us to monitor in real time any adaptive process in response to the Wolbachia strategy. With a combination of in vitro, in vivo and modelling studies, DenWOlution will improve our understanding of DENV evolution and dengue epidemiological dynamics in the population. Furthermore, as many places are implementing the Wolbachia strategy, it is of importance to anticipate the consequences of the interactions between and the reciprocal impact of DENV evolution and Wolbachia intervention. Results arising from this project will inform not only the applications and limitations of the Wolbachia strategy but also any strategy aiming at controlling DENV transmission. DenWOlution will allow us to anticipate the development of future strategies for the control of Ae. aegypti-borne viruses.