Exposure to ultraviolet-B radiation increases the susceptibility of mosquitoes to infection with dengue virus.

By 2100, greenhouse gases are predicted to reduce ozone and cloud cover over the tropics causing increased exposure of organisms to harmful ultraviolet-B radiation (UVBR). UVBR damages DNA and is an important modulator of immune function and disease susceptibility in humans and other vertebrates. The effect of UVBR on invertebrate immune function is largely unknown, but UVBR together with ultraviolet-A radiation impairs an insect immune response that utilizes melanin, a pigment that also protects against UVBR-induced DNA damage. If UVBR weakens insect immunity, then it may make insect disease vectors more susceptible to infection with pathogens of socioeconomic and public health importance. In the tropics, where UVBR is predicted to increase, the mosquito-borne dengue virus (DENV), is prevalent and a growing threat to humans. We therefore examined the effect of UVBR on the mosquito Aedes aegypti, the primary vector for DENV, to better understand the potential implications of increased tropical UVBR for mosquito-borne disease risk. We found that exposure to a UVBR dose that caused significant larval mortality approximately doubled the probability that surviving females would become infected with DENV, despite this UVBR dose having no effect on the expression of an effector gene involved in antiviral immunity. We also found that females exposed to a lower UVBR dose were more likely to have low fecundity even though this UVBR dose had no effect on larval size or activity, pupal cuticular melanin content, or adult mass, metabolic rate, or flight capacity. We conclude that future increases in tropical UVBR associated with anthropogenic global change may have the benefit of reducing mosquito-borne disease risk for humans by reducing mosquito fitness, but this benefit may be eroded if it also makes mosquitoes more likely to be infected with deadly pathogens.

Sustained Wolbachia-mediated blocking of dengue virus isolates following serial passage in Aedes aegypti cell culture.

Wolbachia is an intracellular endosymbiont of insects that inhibits the replication of a range of pathogens in its arthropod hosts. The release of Wolbachia into wild populations of mosquitoes is an innovative biocontrol effort to suppress the transmission of arthropod-borne viruses (arboviruses) to humans, most notably dengue virus. The success of the Wolbachia-based approach hinges upon the stable persistence of the 'pathogen blocking' effect, whose mechanistic basis is poorly understood. Evidence suggests that Wolbachia may affect viral replication via a combination of competition for host resources and activation of host immunity. The evolution of resistance against Wolbachia and pathogen blocking in the mosquito or the virus could reduce the public health impact of the symbiont releases. Here, we investigate if dengue 3 virus (DENV-3) is capable of accumulating adaptive mutations that improve its replicative capacity during serial passage in Wolbachia wMel-infected cells. During the passaging regime, viral isolates in Wolbachia-infected cells exhibited greater variation in viral loads compared to controls. The viral loads of these isolates declined rapidly during passaging due to the blocking effects of Wolbachia carriage, with several being lost all together and the remainder recovering to low but stable levels. We attempted to sequence the genomes of the surviving passaged isolates but, given their low abundance, were unable to obtain sufficient depth of coverage for evolutionary analysis. In contrast, viral loads in Wolbachia-free control cells were consistently high during passaging. The surviving isolates passaged in the presence of Wolbachia exhibited a reduced ability to replicate even in Wolbachia-free cells. These experiments demonstrate the challenge for dengue in evolving resistance to Wolbachia-mediated blocking.