Catalase protects Aedes aegypti from oxidative stress and increases midgut infection prevalence of Dengue but not Zika

Background Digestion of blood in the midgut of Aedes aegypti results in the release of pro-oxidant molecules that can be toxic to the mosquito. We hypothesized that after a blood meal, the antioxidant capacity of the midgut is increased to protect cells against oxidative stress. Concomitantly, pathogens present in the blood ingested by mosquitoes, such as the arboviruses Dengue and Zika, also have to overcome the same oxidative challenge, and the antioxidant program induced by the insect is likely to influence infection status of the mosquito and its vectorial competence. Methodology/Principal findings We found that blood-induced catalase mRNA and activity in the midgut peaked 24 h after feeding and returned to basal levels after the completion of digestion. RNAi-mediated silencing of catalase (AAEL013407-RB) reduced enzyme activity in the midgut epithelia, increased H2O2 leakage and decreased fecundity and lifespan when mosquitoes were fed H2O2. When infected with Dengue 4 and Zika virus, catalase-silenced mosquitoes showed no alteration in infection intensity (number of plaque forming units/midgut) 7 days after the infectious meal. However, catalase knockdown reduced Dengue 4, but not Zika, infection prevalence (percent of infected midguts). Conclusion/Significance Here, we showed that blood ingestion triggers an antioxidant response in the midgut through the induction of catalase. This protection facilitates the establishment of Dengue virus in the midgut. Importantly, this mechanism appears to be specific for Dengue because catalase silencing did not change Zika virus prevalence. In summary, our data suggest that redox balance in the midgut modulates mosquito vectorial competence to arboviral infections.
Author summary Mosquitoes ingest large amounts of blood, a rich and abundant source of energy to sustain egg production. Blood digestion offers challenges to the insect, like managing high concentrations of heme and iron, pro-oxidant and potentially toxic molecules derived from hemoglobin. Mosquitoes and other blood-feeding arthropods have evolved adaptations to overcome this problem, such as the activation of catalase, an antioxidant enzyme that protect tissues against toxic free radicals. Mosquitoes act as important vectors of human diseases because during a blood meal they might also ingest microorganism circulating in our blood, such as dengue and zika virus. The adaptive antioxidant program that protects mosquito tissues against the oxidative challenge imposed by a blood meal might also influences the ability of virus to establish infection and disseminate from the midgut to the salivary glands. We show here that catalase differentially influences the number of infected midguts after mosquitoes were challenged with blood contaminated with virus, being beneficial to Dengue-4 but neutral do Zika, suggesting that redox metabolism may have distinct roles on mosquito vector competence towards different arbovirus.