Suppressing Dengue-2 Infection by Chemical Inhibition of Aedes aegypti Host Factors

摘要: Dengue virus host factors (DENV HFs) that are essential for the completion of infection cycle in mosquito vector and vertebrate represent potent targets transmission blocking. Here we investigated whether known mammalian DENV HF inhibitors could influence arthropod A. aegypti. We evaluated potency bafilomycin (BAF; inhibitor vacuolar H+-ATPase (vATPase)), mycophenolic acid (MPA; inosine-5′-monophosphate dehydrogenase (IMPDH)), castanospermine (CAS; glucosidase), deoxynojirimycin (DNJ; glucosidase) blocking midgut, using various treatment methods included direct injection, ingestion by sugar feeding or blood feeding, silencing target genes RNA interference (RNAi). Injection BAF (5 µM) MPA (25 prior to on virus-infected inhibited titers midgut at 7 days post-infection 56% 60%, salivary gland 14 90% 83%, respectively, while mosquitoes with CAS DNJ did not affect susceptibility virus. Ingestion through a meal together an infectious also resulted degrees inhibition. RNAi-mediated several vATPase subunit IMPDH gene reduced infection, thereby indicating BAF- MPA-mediated inhibition adult most likely occurred these HFs. The route timing administration was essential, after exposure diminished antiviral effect compounds. provide proof-of-principle chemical depletion HFs can be used suppress aegypti mosquitoes, which may translate reduction transmission.