From genes to symbionts: arbovirus-vector interactions

According to WHO, more than 17% of all infectious diseases are vector-borne. This includes arboviruses which are transmitted by arthropod vectors, including mosquitoes, to vertebrates. Factors such as climate change are increasing the risk of emergence and re-emergence of these pathogens across the globe. Viral interactions with the arthropod host are a central topic in arbovirology. These interactions include not only host factors that facilitate virus infection, but also processes that suppress it such as vector antiviral responses, and endosymbionts, all of which can be exploited to develop transmission-blocking control approaches. We will focus on three arboviruses that cause human disease and which are prototypic for the vast majority of vector-borne viruses, selected from the three most important orders/families: Rift Valley fever virus (Bunyavirales), dengue virus (Flaviviridae), and chikungunya virus (Togaviridae). Our aim is to uncover and characterise new factors influencing virus mosquito interactions. Arboviruses are RNA viruses, and this nucleic acid plays a central role in their life cycle as genome and mRNA. Interactions with RNA binding proteins (RBPs) are likely to be as important in arbovirus-vector interactions as they are in vertebrates, but they are far less well understood. Our research will uncover the roles of this heterogeneous group of cellular proteins, RBPs, that have been shown to play critical roles in the viral lifecycle in vertebrate hosts from aiding viral replication and spread to suppressing infection as part of the antiviral defences. This is largely unexplored in vectors yet expected to be highly relevant in interactions with arboviruses. Three work packages will investigate how arboviruses interact with vectors, by studying (i) the complement of cellular RBPs involved in the arbovirus lifecycle; (ii) the properties of RNA interference (RNAi) effectors and associated proteins, critical RBPs of the vector’s antiviral host response; and (iii) host factors, and specifically the contribution of RBPs, that may influence how Wolbachia endosymbionts interfere with arbovirus transmission. We have formed collaborations with The Pirbright Institute (TPI) for development of an RVFV toolkit, and tools for mosquito cells such as a host factor screening system have been established to support this programme. The multi-disciplinarity at CVR makes us ideally placed to deliver this research programme, and the expertise on RBPs opens exciting new avenues. The findings of these studies will lead to new insights into understanding and preventing arbovirus transmission to humans.