Kathryn Rozen-Gagnon

Arthropod-borne viruses (arboviruses) are continually emerging around the globe and cause ~100 million infections/year. Arboviruses are almost exclusively RNA viruses that must infect arthropod vectors, such as mosquitoes, for transmission to their human hosts. Intriguingly, while humans become sick but often clear the virus, mosquitoes remain infected for life, happily feeding and infecting new hosts. Despite the enormous global disease burden imposed by arboviruses, we lack a detailed understanding of how arbovirus RNA genomes succeed in these divergent organisms.

Upon entering a human or mosquito cell, arbovirus RNA becomes a potential substrate for interactions with wildly disparate host RNAs and RNA binding proteins (RNA networks). These interactions may either promote or hinder the viral life cycle. However, our understanding of arbovirus infections in the mosquito vector is impeded by lack of experimental and informatic resources. My lab develops sophisticated methods in mosquito cells and mosquitoes to address arbovirus biology holistically in both humans and mosquitoes. We apply a comparative approach to understand how arboviruses engage a group of essential RNA networks conserved in both humans and mosquitoes: RNA interference (RNAi) networks.

RNAi globally modulates gene expression in both human and mosquito cells. However, specific RNAi effectors will differ dramatically in each organism. We use systems biology and experimental virology to uncover how arboviruses such as chikungunya, Zika, and West Nile engage RNAi networks to manipulate pro- or anti-viral cellular pathways in humans and mosquitoes.

Importantly, RNAi is the main mosquito defense against arboviruses. Yet, to-date, we have little understanding of which antiviral effectors are functional, and why. The transcriptomics methods we’ve developed in the mosquito allow us to take a snapshot of the functional mosquito immune response. We apply these methods to understand whether RNA-based immunity facilitates persistence and immune memory in the mosquito, and how an arbovirus might escape the mosquito immune response.