A common strategy for counteracting antiviral mechanisms in human and mosquito by CHIKV nsP1

With limited coding capacity viruses employ host cell factors to create a conducive intracellular environment for their optimal replication. To this end viral proteins engage cellular proteins to modulate metabolic pathways, dysregulate cell cycle progression and counteract innate antiviral mechanisms. For successful survival, chikungunya virus, as an arthropod-borne virus, is required to replicate in the very distinct cellular environments of both the mammalian host and the insect vector. To gain insight into the replication mechanism of chikungunya virus in both organisms we recently identified the protein interaction network of CHIKV proteins with cellular factors in both human and mosquito cells. Engagement of CRLs by viral proteins has been described as a mechanism to counteract innate immune processes by targeting cellular antiviral factors for proteasomal degradation. Chikungunya virus non-structural protein 1 (nsP1) was found to specifically associate with various members of cullin Ring ubiquitin ligase complexes (CRLs) in both human and mosquito cells as well as with known antiviral factors. We hypothesize that CHIKV nsP1 counteracts antiviral factors through engagement of cullin Ring ligases in both human and mosquito cells. The proposed project will provide insight in a shared viral mechanism in both organisms, serve as basis for future exploration of this concept and allow expansion of our tools to study arboviral replication in mosquitos.