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.

Intrinsic factors driving mosquito vector competence and viral evolution: a review

“…In contrast, there was a moderate salivary gland escape barrier when mosquitoes were infected with ZIKV or CHIKV but not DENV. The influence of genetic factors was also more pronounced when viral titers were low (Novelo et al, 2023). Taken together, mounting evidence supports an underlying genetic basis for VC, but that is variable across mosquito and virus species.…”

“…Even within the same isofemale line (family), mosquito genetic background may be influencing VC for different viruses in disparate ways. Novelo et al investigated the impact of genetic variation on VC for DENV and CHIKV by employing a modified full-sibling design using viral RNA quantity as a proxy value for VC (Novelo et al, 2023). Mosquitoes from 37 families were reared separately; half of the siblings from each family were challenged with CHIKV and the other half DENV.…”

The High Capacity of Brazilian Aedes aegypti Populations to Transmit a Locally Circulating Lineage of Chikungunya Virus

“…In Brazil, the main vectors associated with the transmission of these CHIKV lineages are the mosquitoes Aedes aegypti and Aedes albopictus , both of which are widely distributed across the country [ 7 ]. Previous studies have shown that these two Aedes species are competent vectors for both the ECSA and Asian lineages across different regions of the world [ 13 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ]. However, in Brazil, the impact of locally circulating CHIKV genotypes and specific combinations of local Aedes aegypti populations on the vector competence has not been thoroughly examined.…”

High capacity of BrazilianAedes aegyptipopulations to transmit a locally circulating lineage of Chikungunya virus

“…In Brazil, the main vectors associated with the transmission of these CHIKV lineages are the mosquitoes Aedes aegypti and Aedes albopictus, both of which are widely distributed across the country [14,18,20,29]. Previous studies have shown that these two Aedes species are competent vectors for both the ECSA and Asian lineages across different world regions [15,[29][30][31][32][33][34][35][36].…”