Tolerance to persistent cell-fusing agent virus infection in Aedes aegypti mosquitoes correlates with maintenance of lipid reserves

Background: Resistance and tolerance are two distinct, but complementary defense strategies to mitigate the effects of a viral infection. Resistance limits viral load. Tolerance minimizes health impacts without directly acting on viruses. In Aedes spp. mosquitoes, which are vectors of the public-health relevant Zika, dengue, yellow fever, and chikungunya viruses, the predominance of one mechanism over the other has ecological and evolutionary implications because resistance supports an arm-race between mosquitoes and viruses, whereas tolerance favors neutral or positive effects on viruses. While resistance mechanisms have been amply studied, tolerance mechanisms are poorly understood in arboviral vectors. 

Results: We chose to examine the infection dynamics, resistance, and tolerance to the insect-specific virus (ISV) cell-fusing agent virus (CFAV) in two laboratory populations of Ae. aegypti, Liverpool (LVP), and ZacPanda (ZacP) because field-collected mosquitoes are more frequently infected with ISVs than arboviruses. We found that CFAV establishes lifelong infections, eliciting RNA interference (RNAi) in both strains. However, we observed differences in tolerance, with LVP mosquitoes exhibiting lower tolerance to CFAV than ZacP mosquitoes. We further demonstrate that the lower tolerance of LVP mosquitoes correlates with dysregulation of energy reserves, with a higher content of proteins and lower of lipids following CFAV infection. 

Conclusions: Our findings underscore the importance of tolerance mechanisms in supporting persistent viral infections in mosquitoes. By regulating energetic resources, tolerance may play a crucial role in shaping virus–host interactions. These results highlight the need for further investigation into tolerance strategies, given their potential impact on viral transmission dynamics and vector control approaches.