Mosquito Saliva May Inhibit Dengue Virus Transmission

Researchers at Central Michigan University (CMU) have found that proteins in the saliva of Aedes aegypti mosquitoes bind to Dengue virus and inhibit disease transmission to human cells and mice.

The proteins in question, from the D7 family, have long been known to be present in mosquito saliva and are believed to assist in the blood feeding process following a bite. The researchers believe that antibodies to D7 proteins, which are present in humans who have sustained bites, may actually facilitate Dengue transmission and increase disease severity.

Their findings were published on September 15 by the journal PLOS Neglected Tropical Diseases.

“Although individuals living in endemic regions are all exposed to Aedes aegypti bites, their adaptive immune systems may respond differently to mosquito saliva,” study co-author Michael J. Conway, PhD, assistant professor of microbiology at CMU’s College of Medicine told Contagion. “Mosquito saliva is a complex mixture that together appears to enhance infection and disease. However, our study suggests that some components may also inhibit infection. Therefore, it is theoretically possible that some individuals have specific immune responses to mosquito saliva proteins that make them more or less susceptible to infection.”

Dr. Conway emphasized that “more work needs to be done to profile the immune response to mosquito bites and determine if immunoreactivity to specific saliva proteins can modify infection and disease,” and that his lab is engaged in research to address this knowledge gap. To date, he and his colleagues have been active in efforts to find ways to reduce Dengue virus transmission. They have been exploring the potential role for mosquito saliva or midgut proteins in interventions (ie, vaccines) designed to block transmission. According to Dr. Conway, this approach has several advantages over vaccines based on viral proteins because it does not need to be modified to be effective against different strains of the virus.

“The goal of my laboratory is to identify virus-vector-host interactions that can be exploited to break the transmission cycle of mosquito-borne flaviviruses,” he said. “A major focus is to identify the mosquito saliva proteins that are responsible for enhancing infection in the host. These proteins could be used as a vaccine to block saliva-mediated transmission enhancement. Because D7 protein appears to inhibit virus infection, we are interested in the mechanism of inhibition, so that we can adapt this mechanism into new therapeutics to limit the severity of disease.”

In earlier studies, Dr. Conway and his team have isolated proteins from the salivary glands of the Aedes aegypti, which is known to carry Dengue, Zika, and Chikungunya, and tested them to assess whether they aided or inhibited transmission. For this study, they compared uninfected Aedes aegypti mosquitoes with those infected with Dengue and found that infected mosquitoes had increased levels of D7 proteins in their salivary glands. They also noted that insect cells treated with D7 proteins before and during Dengue exposure had significantly reduced levels of Dengue RNA.

In experiments with mice, meanwhile, they found that the presence of D7 significantly reduced the levels of Dengue RNA both at the exposure site and in nearby lymph nodes. They also noted that D7s can bind Dengue virus’s envelope protein.

According to Dr. Conway, these findings suggest that, “it may be possible to redirect the host humoral immune response in the future so that less anti-Aedes aegypti D7 antibody is made, which would increase the antiviral efficacy of the protein. We are making progress towards understanding how individual components in vector saliva modify disease transmission. We should soon have a candidate saliva protein that is responsible for enhancing disease transmission that we can develop into a transmission blocking vaccine.”

Brian P. Dunleavy is a medical writer and editor based in New York. His work has appeared in numerous healthcare-related publications. He is the former editor of Infectious Disease Special Edition.