Research
Published on December 11, 2018 | Updated on December 11, 2018

DENGEVOLOMICS Project

Functional study of the genetic interactions between Dengue virus and its mosquito vector by experimental evolution

Leaders : Marlène Dreux (CIRI) and Bastien Boussau (LBBE)

The dengue virus (DENV) is an RNA virus that causes the most prevalent arthropod-borne viral disease with an estimated 390 million human infections yearly. The risks of infection are rising due to global warming and the consequent increased dissemination of its vector, mosquitoes from the Aedes species. DENV infection in humans causes dengue fever and severe pains, along with life-threatening forms of hemorrhagic fever and shock syndrome. While neither therapeutics nor a vaccine are currenty available, the most promising strategies to control the epidemic target the mosquitoes.
Especially, recent evidence demonstrates the great potential of the introduction in wild populations of mosquitoes infected by the maternally transmitted bacteria Wolbachia (Wol) to combat DENV transmission. Indeed, the presence of Wol in the mosquito potently restricts DENV replication, notably by exacerbating the immune response. Yet, very little is known on the immune response against DENV infection in its vector. Importantly, DENV has such a high mutation rate that it can rapidly adapt to its host and acquire escape mechanisms from immune responses or control strategies. As such, viral escape from transmisison control strategies targeting the vector (e.g., Wol co-infection) remains to be studied.
The DENGEVOLOMICS project aims at identifying determinants in the viral genome that govern the interactions between the virus and the host environment in mosquito cells, and the evolutionary mechanisms underlying viral escape. We propose an unbiased genomic approach, based on the study of the evolution of the entire viral quasi-species (i.e, populations of highly diverse genomes) in response to experimental modulations of a controlled cellular environment, by combining new methods of high throughput sequencing and bioinformatics. The studies are focused on DENV interactions with the mosquito defense responses and the restriction by Wol co-infection.

Co-leaders : Marlène Dreux, team "Enveloppes virales, vecteurs et réponse innée" (CIRI) and Bastien Boussau, team "Bio-informatique et génomique évolutive" (LBBE).
Collaborative partners: Mathilde Paris, Developmental Biology Institute (University of Marseille - Luminy).
Project duration :
3 years
Financing :
Post-doc fellowship and consumable money
Post-doctoral fellow:
Kassian Kobert