Aedes spp. mosquitoes are important vectors of disease as they inject pathogen-containing saliva into a vertebrate host. Schmid et al. showed that salivary gland extract (SGE) augmented dengue virus (DENV) infection in the presence of enhancing serotype cross-reactive antibodies (which are non-neutralizing antibodies that do not protect against a different serotype and instead enhance subsequent infection), leading to severe disease and death. Furthermore, during antibody-dependent enhancement, SGE increased viral titres in the skin, augmented infection of dermal dendritic cells and macrophages, and accelerated the migration and recruitment of immune cells to the skin and lymph nodes. The authors also found that SGE disrupts endothelial barrier function in vitro and endothelial permeability in vivo. Finally, surgically removing the body site of inoculation rescued mice from severe disease, whereas this protective effect was abolished in the presence of SGE, which suggests that SGE affects systemic infection with DENV. In a second study, Liu et al. reported that the flavivirus non-structural protein 1 (NS1) has a crucial role in the acquisition of DENV and Japanese encephalitis virus (JEV) by mosquito vectors. During infection, NS1 is abundantly present in sera of patients and has been implicated in viral pathogenesis. The authors of this study now report that NS1 increases virus transmission from infected mice and that this effect is blocked following the inoculation of infected hosts with anti-NS1 antibodies. Importantly, the authors found that NS1 suppresses the expression of immune-related genes in the mosquito midgut, thereby enabling the virus to overcome the gut immune barrier. Finally, immunization of mice with a modified DENV2 NS1 in which immunogenic regions were deleted led to decreased DENV acquisition by mosquitoes and increased survival rates in infected mice compared with full-length NS1, which suggests that this approach might provide a new vaccination strategy.