Researchers at the University of South Carolina School of Medicine and the Central Michigan University College of Medicine identified a protein required for the Dengue fever virus to infect mosquitoes. This protein could be used as part of a Dengue fever vaccine.
Dengue virus is transmitted to humans by the Aedes
mosquito. The virus infects nearly 400 million people each year, but over 2 billion live in areas where the virus is endemic. Symptoms of Dengue fever
include severe headache and pain behind the eyes, muscle and joint pain, bleeding from the nose and gums, and low white cell count. Some strains of the virus cause a more serious hemorrhagic fever that kills roughly 22,000 people each year.
The researchers previously identified 203 mosquito genes that were significantly upregulated during Dengue virus infection. They further identified 20 genes that, when silenced, reduced infection in mosquitoes cells by more than 60%. In the current study, published in PLOS Pathogens
, the group focused on one of those 20 proteins, the cysteine-rich venom protein called CRVP379.
The group found that Dengue virus-infected mosquito cells upregulated CRVP379 nearly 800-fold. CRVP379 is expressed in the mosquito gut where it interacts with another protein, prohibitin, that likely acts as a viral receptor. In one experiment, researchers fed mosquitoes an antibody to CRVP379 to block its interaction with other proteins. As a result, Dengue virus was unable to infect the mosquitoes.
CRVP379 is an excellent vaccine candidate because it is not similar to human proteins. This means there is little risk of the vaccine causing an autoimmune response. In addition, CRVP379 antibodies have been detected in the blood of people with Dengue fever, meaning that the body effectively makes antibodies to the protein. CRVP379 is also upregulated when mosquitoes are infected with West Nile and Yellow Fever viruses, so a Dengue vaccine could protect against these viruses as well.
Sources: PLOS Pathogens
, Science Daily
, CDC, Wikipedia