PIWI-interacting RNAs at the interface of virus-host conflicts in Aedes aegypti mosquitoes

Background: The mosquito Aedes aegypti transmits viruses with pandemic potential but is also host to a large repertoire of mosquito-specific viruses and endogenous retroviruses.

These viruses may invade the ovaries and eventually the oocyte to be transmitted from mother to offspring and to expand in the population.

This transmission route exposes them to the specific host defense mechanisms of the ovary, which they must overcome to ensure onward transmission.

This intriguing virus–host conflict is crucial for virus evolution and ecology and for host reproduction and survival, but has thus far not been studied.

Hypothesis: I hypothesize that a specific class of small RNAs, called PIWI-interacting RNAs (piRNAs), are essential for protection of the mosquito germline from virus infection.Aim: My goal is to define the role of the piRNA pathway as a host defense system against RNA viruses, endogenous retroviruses, and other genomic parasites, and to identify viral counter-defense mechanisms.

Additional to these fundamental aims, we will reprogram the piRNA pathway to induce resistance against pathogenic viruses in mosquitoes.

Approach: This interdisciplinary project c¬ombines powerful genetic, genomic, and proteomic approaches at the intersection of virology, RNA biology, and entomology.

Of particular importance, we will establish urgently needed tools for tissue-specific gene inactivation in vivo to define the functions of the expanded PIWI gene family of mosquitoes.Importance and Innovation: ERC project PIWIdefense will be the first to define host defense functions of the piRNA pathway in the germline of a major vector mosquito.

The project generates unprecedented insights into the fundamental processes that shape the fascinating virus–host conflicts in mosquitoes.

In addition, the project establishes a novel approach that can be translated into mosquito-centered intervention strategies against arthropod-borne viruses.