Arbovirus Persistence In Mosquitoes: The Role Of Translation Control

Abstract

Mosquito-transmitted viruses infect both vertebrate hosts, where they cause acute disease, and mosquito vectors, where they establish persistent infection. While persistence in mosquito cells is essential for transmission, the mechanisms enabling sustained viral protein expression without compromising mosquito fitness remains poorly understood. Using chikungunya virus (CHIKV) as a model, this thesis addresses this fundamental question through a temporal, genome-wide analysis of transcription, translation, and tRNA modifications in both mosquito cell culture and in vivo. We find that persistence is characterized by a dynamic host-virus translational balance, wherein viral RNA translation is selectively repressed, allowing sufficient viral protein expression for transmission while preserving host protein synthesis and fitness. Crucially, this repression involves a tRNA modification–dependent mechanism that modulates translation in response to virus-induced metabolic stress. These findings reveal a novel strategy by which mosquito-transmitted viruses fine-tune the translational landscape of their vector to support long-term persistence and successful transmission.