Aedes aegypti SNAP and a calcium transporter ATPase influence dengue virus dissemination

Dengue virus (DENV) is a flavivirus that causes marked human morbidity and mortality worldwide, and is transmitted to humans by Aedes aegypti mosquitoes. Habitat expansion of Aedes, mainly due to climate change and increasing overlap between urban and wild habitats, places nearly half of the world's population at risk for DENV infection. After a bloodmeal from a DENV-infected host, the virus enters the mosquito midgut. Next, the virus migrates to, and replicates in, other tissues, like salivary glands. Successful viral transmission occurs when the infected mosquito takes another blood meal on a susceptible host and DENV is released from the salivary gland via saliva into the skin. During viral dissemination in the mosquito and transmission to a new mammalian host, DENV interacts with a variety of vector proteins, which are uniquely important during each phase of the viral cycle. Our study focuses on the interaction between DENV particles and protein components in the A. aegypti vector. We performed a mass spectrometry assay where we identified a set of A. aegypti salivary gland proteins which potentially interact with the DENV virion. Using dsRNA to silence gene expression, we analyzed the role of these proteins in viral infectivity. Two of these candidates, a synaptosomal-associated protein (AeSNAP) and a calcium transporter ATPase (ATPase) appear to play a role in viral replication both in vitro and in vivo, observing a ubiquitous expression of these proteins in the mosquito. These findings suggest that AeSNAP plays a protective role during DENV infection of mosquitoes and that ATPase protein is required for DENV during amplification within the vector. Author summary Dengue is a mosquito-borne viral disease whose incidence has increased dramatically (>30-fold) in recent years, alongside the geographical expansion of Aedes mosquitoes. Dengue is currently one of the most important neglected tropical diseases, and its transmission is strongly influenced by rainfall, temperature, urbanization and distribution of the principal mosquito vector Aedes aegypti. Vector control strategies are being implemented to reduce the expansion of this disease, but still there is a great need for better therapeutics and preventive vaccines against dengue and other flaviviruses. Flaviviruses create complex virus-host and virus-vector interactions. The interactions between viral particles and protein components in the vector are not completely understood. In this work we characterize how two mosquito proteins, AeSNAP and ATPase, influence DENV viral dissemination within A. aegypti, using both in vitro and in vivo models. These results suggest that anti-vector measures that target specific mosquito molecules may represent promising alternatives to traditional countermeasures against dengue virus spread.

Automated summary

Dengue virus is a flavivirus transmitted by Aedes aegypti mosquitoes, placing nearly half of the world's population at risk for infection. The study identified two mosquito proteins, AeSNAP and ATPase, that play a role in DENV viral dissemination, suggesting potential targets for combating dengue.