The salivary gland is the organ that ultimately transmits an arbovirus from an infected mosquito into her vertebrate host. Salivary gland infection barriers (SGIBs) and salivary gland escape barriers (SGEBs) determine whether the saliva of a mosquito will contain sufficient virus to overcome the vertebrate immune system. SGIBs are manifest as the absence of detectable virus in the salivary glands of mosquitoes that have a disseminated viral infection (as determined by bioassay of pulled legs or smashed heads). There are large numbers of studies that document SGIBs for bunyaviruses and flaviviruses. SGEBs on the other hand are manifest as the absence of detectable virus in the saliva of mosquitoes that have infected salivary glands (as determined by bioassay of dissected glands). In contrast to SGIBs, there are very few studies that document SGEBs in mosquitoes and those have only examined bunyaviruses. Furthermore these SGEB studies were not performed in genetically ?tractable? mosquito species that can be easily colonized from the field, reared in the lab, crossed as single pairs and have an abundance of genetic markers. Because of this deficiency we have little understanding of whether there is a genetic basis for SGEBs or whether they are random, subject to a few or many ?environmental? factors. The results of this study will indicate whether there are genetic factors in the mosquito which, if manipulated through transgenics or pharmaceuticals, could interfere with the ability of the mosquito to transmit an arbovirus. Alternatively if mosquito genetics accounts for very little of the ability of the mosquito to transmit arboviruses then this is unlikely to be a fruitful approach. PI Black's earlier work on the quantitative genetics of DENV-2 in Ae. aegypti midgut infection and escape barriers indicated that 40% of the variation was due to genetic effects and 60% was due to environmental effects. To date, many genes have been identified that affect tissue barriers to DENV-2 infections but many environmental effects (including viral genotype) have also been identified. Will the same hold true from SGIBs and SGEBs?
Dengue viruses infect 50-100 million people annually resulting in up to 500,000 dengue hemorrhagic fever cases. More than 700 chikungunya cases have been reported from US states last year. Zika virus disease outbreaks were reported in South America for the first time. These viruses are transmitted by the mosquito, Aedes aegypti. This is a proposal to understand how the mosquito salivary glands affect transmission of these important arboviruses.
