Profiling lipidomic changes in dengue-resistant and dengue-susceptible strains of Colombian Aedes aegypti after dengue virus challenge

The mosquito Aedes aegypti is the primary vector for all four serotypes of dengue viruses (DENV1-4), which infect millions across the globe each year. Traditional insecticide programs have been transiently effective at minimizing cases; however, insecticide resistance and habitat expansion have caused cases of DENV to surge over the last decade. There is an urgent need to develop novel vector control measures, but these are contingent on a detailed understanding of host-parasite interactions. Here, we have utilized lipidomics to survey the profiles of naturally DENV-resistant (Cali-MIB) or susceptible (Cali-S) populations of Ae. aegypti, isolated from Cali, Colombia, when fed on blood meals containing DENV. Control insects were fed on a DENV-free blood meal. Midguts were dissected from Cali-MIB and Cali-S females at three time points post-infectious blood meal, 18, 24 and 36h, to identify changes in the lipidome at key times associated with the entry, replication and exit of DENV from midgut cells. We used principal component analysis to visualize broad patterns in lipidomic profiles between the treatment groups, and significance analysis of microarray to determine lipids that were altered in response to viral challenge. These data can be used to identify molecules or metabolic pathways particular to the susceptible or refractory phenotypes, and possibly lead to the generation of stable, DENV-resistant strains of Ae. aegypti.Author summary: Dengue virus (DENV) is a mosquito-transmitted pathogen that can lead to severe complications for infected humans, including hemorrhagic fever or death. Approximately 390 million people are infected with DENV yearly, and reported cases are rising. Currently, we do not have any effective treatments for DENV infection in humans and primarily rely on mosquito control programs to limit transmission. Insecticide-resistant populations, however, are emerging, and there is an urgent need to develop novel methods to control case numbers. We have reported previously on two populations of Ae. aegypti, the primary vector for DENV, in Cali, Colombia, which are either permissive (Cali-S) or refractory (Cali-MIB) to viral replication. Here we report the use of highly sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) to observe changes in the lipidome of the midguts of these strains after challenge with DENV. Using comparative statistics, we identified lipid features significantly altered in the refractory (Cali-MIB) strain after DENV bloodmeal. The compounds identified in this screen could represent molecular targets for future research into developing stable DENV-resistant Ae. aegypti populations.