Breaking mosquito tolerance to arbovirus infections by manipulating retrotransposons

"Diseases spread by the mosquitoes Aedes aegypti and Aedes albopictus are rapidly increasing due to climate change, urbanization, and international travel. These mosquitoes are responsible for spreading dangerous diseases like yellow fever, dengue, and Zika. Insecticides, which were once effective, are becoming less so due to mosquito resistance and the environmental damage they cause. Therefore, it is necessary to find new control methods. Mosquitoes can tolerate viral infections without becoming sick, allowing them to continue spreading viruses. Unlike resistance (which eliminates the virus), this tolerance does not kill the virus. Reducing this tolerance could interrupt the virus lifecycle within the mosquito, thus preventing transmission. The ArboRetro project aims to exploit this mechanism to render mosquitoes incapable of tolerating viruses and therefore unable to transmit them. Our previous research has shown that certain genetic elements called retrotransposons produce virus-derived DNA molecules that help enhance the antiviral response in flies like Drosophila. In mosquitoes, inhibiting the activity of these retrotransposons with drugs causes the death of infected mosquitoes, proving their role in viral tolerance. ArboRetro aims to use this discovery to prevent mosquitoes from transmitting viruses. The project is based on a collaboration between three partners: Maria-Carla Saleh's lab, which studies antiviral immunity, Gael Cristofari's lab, which focuses on retrotransposon biology, and Louis Lambrechts' lab, which studies mosquito biology. ArboRetro will use advanced technologies, including base editing and long-read sequencing, to genetically inactivate the retrotransposons responsible for viral tolerance and assess the consequences. The objectives of the project are: Identify and genetically inactivate these specific retrotransposons. Study how this inactivation affects virus transmission. Examine the presence of this viral tolerance mechanism in natural mosquito populations. By achieving these objectives, ArboRetro will pave the way for a sustainable and effective strategy to control mosquito-borne viruses and reducing their impact on global health."