Dengue and chikungunya virus loads in the mosquito Aedes aegypti are determined by distinct genetic architectures

Abstract

Aedes aegypti is the primary vector of the arboviruses dengue (DENV) and chikungunya (CHIKV). These viruses exhibit key differences in their vector interactions, the latter moving more quicky through the mosquito and triggering fewer standard antiviral pathways. As the global footprint of CHIKV continues to expand, we seek to better understand the mosquito’s natural response to CHIKV—both to compare it to DENV:vector coevolutionary history and to identify potential targets in the mosquito for genetic modification. We used a modified full-sibling design to estimate the contribution of mosquito genetic variation to viral loads of both DENV and CHIKV. Heritabilities were significant, but higher for DENV (40%) than CHIKV (18%). Interestingly, there was no genetic correlation between DENV and CHIKV loads between siblings. These data suggest Ae. aegypti mosquitoes respond to the two viruses using distinct genetic mechanisms. We also examined genome-wide patterns of gene expression between High and Low CHIKV families representing the phenotypic extremes of viral load. Using RNAseq, we identified only two loci that consistently differentiated High and Low families: a long non-coding RNA that has been identified in mosquito screens post-infection and a distant member of a family of Salivary Gland Specific (SGS) genes. Interestingly, the latter gene is also associated with horizontal gene transfer between mosquitoes and the endosymbiotic bacterium Wolbachia. This work is the first to link the SGS gene to a mosquito phenotype. Understanding the molecular details of how this gene contributes to viral control in mosquitoes may, therefore, also shed light on its role in Wolbachia.