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

Abstract

BackgroundDigestion 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 findingsWe 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/SignificanceHere, 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.

Control of Redox Homeostasis in Tick Blood Feeding

“…In Ixodes ricinus tick, it has been reported that there are more sulfotransferase transcripts in tick midgut after blood feeding than before [67]. The same pattern was observed with catalase transcripts in Aedes aegypti [56]. In Dermacentor variabilis tick, blood intake promotes the up-regulation of glutathione-S transferase (GST) transcription in midgut and ovary [24].…”

Molecular Basis for Arbovirus Transmission by <b><i>Aedes aegypti</i></b> Mosquitoes

“…Nonetheless, protecting measures such as releasing catalase might facilitate infection of the epithelial cells in the midgut by viruses like DENV [91, 92]. Nevertheless, more studies will be necessary to establish the overall role of these events in arboviruses.…”

Hydrogen Medicine Therapy: An Effective and Promising Novel Treatment for Multiple Organ Dysfunction Syndrome (MODS) Induced by Influenza and Other Viral Infections Diseases?

“…Recent studies revealed that intraperitoneal injection of hydrogen-rich saline has surprising anti-inflammation, anti-oxidant, anti-apoptosis effects and protected organism against polymicrobial sepsis injury, acute peritonitis injury both by reducing oxidative stress and via decreasing mass proinflammatory responses. It is also well known that the majority of viral -induced tissue damage and discomfort are mainly caused by an inflammatory cytokine storm and oxidative stress rather than by virus itself [3][4][5]. Studies have shown that suppressing the cytokine storm and reducing oxidative stress can significantly alleviate the symptoms of influenza and other severe viral infections diseases [3][4][5][6][7].…”

“…In the past decade, molecular hydrogen was considered a surprising agent, which can significantly reduce oxidative stress by selectively reducing hydroxyl radical Hutaohong2010@163.com (•OH) and Peroxynitrite (ONOO-) [1,[8][9][10]. It has recently been revealed that hydrogen can both down-regulate expression of oxidative-related genes and pro-inflammatory cytokine genes directly and indirectly [2][3][4][5]11,12]. Oxidative stress and systemic inflammatory response syndrome have been confirmed to play critical roles in tissue and organ damages after polymicrobial sepsis injury, acute peritonitis injury, and peritonitis, which can develop into lethal sepsis with inappropriate treatment [13,14].…”

“…It is also well known that the majority of viral -induced tissue damage and discomfort are mainly caused by an inflammatory cytokine storm and oxidative stress rather than by virus itself [3][4][5]. Studies have shown that suppressing the cytokine storm and reducing oxidative stress can significantly alleviate the symptoms of influenza and other severe viral infections diseases [3][4][5][6][7]. However, none of the studies have been focused on the solution as an anti-virus infection therapy yet.…”