Global 5-methylcytosine-RNA disruption reduces the vectorial competence to DENV2 of heatwave-exposed Aedes aegypti mosquitoes

Heatwaves are an increasingly common environmental event linked with climate change. Abnormally high heatwave temperatures can affect several mosquito vector traits that are determinants of pathogen transmission. Understanding how these mosquitoes adapt to high heat is vital for global public health. RNA methylation, a key cellular mechanism in stress response and adaptation, remains understudied in mosquito vector competence and heat stress responses. This study investigates the role of RNA methylation in mosquito responses to heatwaves and its influence on DENV2 vector competence. Heatwave-exposed and DENV-infected mosquitoes presented lower survivorship and lower antiviral transcriptional response, developed high infection rates, and increased the life expectancy of infected mosquitoes during the period of highest virus transmissibility. In contrast, inhibition of RNA methylation in heatwave-treated mosquitoes increased survivorship and the antiviral transcriptional response, reducing infection prevalence from 78% to 37%. These results indicate that the RNA methylation background in mosquitoes favors vector competence for DENV2 during a heatwave exposure, and points towards possible interventions to countermeasure the effect of climate change on DENV transmission.