Despite decades of attempts at disease control, dengue remains one of the most significant mosquito-borne arboviral diseases, causing an estimated 390 million infections annually. While studies of molecular interactions between DENV and Ae. aegypti have paved a way for the development of alternative DENV control strategies, this field is still relatively understudied. Here, we used multiple molecular tools to study interactions between the virus and Ae. aegypti, as well as to identify DENV host and restriction factors. First, we have developed genetically modified mosquitoes with increased activity of the JAK/STAT pathway, and showed that these transgenic mosquitoes could inhibit DENV infection. Through microarray-based transcriptomic comparisons, we identified candidate DENV host and restriction factors and confirmed their function through RNAi. Second, we compared transcriptomic profiles of a panel of field-derived and laboratory Ae. aegypti strains with different DENV susceptibility. Through RNAi-mediated gene silencing, we have shown that basal level of immune activity, and expression level of host factors are important determinants for DENV susceptibility. Lastly, through a study of transcriptomic datasets comparing DENV-infected and uninfected Ae. aegypti, we identified and characterized lipid binding protein families, ML and NPC1, as host factors for DENV replication in Ae. aegypti
