Dehydration-induced Ae-Aper50 regulates midgut infection in Aedes aegypti mosquitoes

Climate change is predicted to increase the spread of mosquito-borne viruses, but genetic mechanisms underlying the influence of environmental variation on the ability of insect vectors to transmit human pathogens is unknown. In response to a changing climate, mosquitoes will experience longer periods of drought. An important physiological response to dry environments is the protection against dehydration, here defined as desiccation tolerance. While temperature is known to impact interactions between mosquito and virus, the role of dehydration remains unknown. We identified two genetically diverse lines of the mosquito Aedes aegypti, a major arbovirus vector, with marked differences in desiccation tolerance. To determine the genetic response to dehydration between these contrasting lines, we compared gene expression profiles between desiccant- and non-desiccant-treated individuals in both the desiccation-tolerant and -susceptible lines by RNAseq. Gene expression analysis demonstrated that several genes are differentially expressed in response to desiccation stress between desiccation-tolerant and -susceptible lines. The most highly expressed transcript under desiccation stress in the desiccation-susceptible line encodes a peritrophin protein, Ae-Aper50. Peritrophins play a crucial role in peritrophic matrix formation in the mosquito midgut after a bloodmeal. Gene silencing of Ae-Aper50 by RNAi demonstrated that expression of Ae-Aper50 is required for survival of the desiccation-susceptible line under desiccation stress, but not for the desiccation-tolerant line. Moreover, the knockdown of Ae-Aper50 resulted in higher Zika virus (ZIKV) infection rates in the desiccation-tolerant line and increased ZIKV viral replication in the desiccation susceptible line, and higher chikungunya virus (CHIKV) infection rates in the desiccation-tolerant line. Altogether, these results provide a link between protection against desiccation and midgut infection, which has important implications in predicting how climate change will impact mosquito-borne viruses.