Washington: Researchers have identified a protein that could be targeted to prevent transmission of the dengue virus, an advance that could lead to the development of a vaccine against the deadly infection. There is currently no approved specific treatment or vaccine for dengue fever, and an estimated 2 billion people are at risk for being bitten by Aedes mosquitoes and infected with the dengue virus (DENV).
Researchers have now found a candidate target for a transmission-blocking vaccine that interferes with virus infection of the mosquito after it feeds on the blood of infected hosts.
Researchers from the University of South Carolina School of Medicine and Central Michigan University College of Medicine in US, studied mosquito genes up-regulated during DENV infection as some of them are likely required for virus survival or infection.
Having previously identified a number of such genes, they here focused on one of them – which they termed CRVP379 – that codes for a putative cysteine-rich venom protein.
The researchers found that CRVP379 is required during DENV infection in mosquito cells and in live mosquitoes, and that there is a direct correlation between the amount of CRVP379 expressed in the mosquito gut (where infection initiates) and the level of DENV infection in the gut and in whole mosquitoes.
They went on to show that CRVP379 interacts with a protein called prohibitin that is a putative DENV receptor in mosquitoes. When the researchers fed Aedes mosquitoes antibodies able to recognise CRVP379, potentially blocking the interaction of the protein with either DENV or prohibitin, they found that this inhibits DENV infection of the mosquitoes.
“These results further our understanding of DENV pathogenesis in the mosquito vector and highlight a potential target protein for the creation of a DENV transmission-blocking vaccine to break the host-vector transmission cycle,” the researchers said.
Discussing further the suitability of CRVP379 as a potential vaccine target, the researchers noted that the protein lacks similarities to human proteins (which when present could lead to undesired auto immune reactions against a potential human vaccine).
It is also up-regulated when mosquitoes are infected with two related viruses, West Nile virus and Yellow Fever virus, and hence might be useful in blocking transmission of these viruses as well. Moreover, researchers have been able to detect antibodies against CRVP379 in human blood samples, demonstrating that the protein is able to elicit an immune response in humans. Researchers are currently investigating whether levels of these antibodies correlate with protection against DENV infection and disease severity upon infection. The study was published in the journal PLOS Pathogens.