Interrupting the transmission cycle of dengue virus

Dengue virus-infected cells Dengue virus is responsible for serious human disease worldwide. The World Health Organization estimates that over 2 billion people are at risk for this disease. There are currently no vaccines or specific antiviral medications currently available for dengue virus infection. The virus is transmitted to humans by infected mosquitoes during feeding and probing. By examining the effects of virus infection on gene expression, and interactions between virus and vector, it may be able to find new targets for prevention and treatment.

A new paper looks at a mosquito protein, CRVP379, whose expression was highly increased during dengue virus infection in mosquitoes. There is a requirement for CRVP379 during dengue virus infection in the mosquito and a correlation between the levels of CRVP379 and levels of infection. The results indicate that the protein may be acting with a putative dengue virus receptor in the mosquito, prohibitin protein. These data also suggest that blocking CRVP379 function may be used to block dengue virus infection in the mosquito.

Dengue Virus Infection of Aedes aegypti Requires a Putative Cysteine Rich Venom Protein. (2015) PLoS Pathog 11(10): e1005202. doi: 10.1371/journal.ppat.1005202
Dengue virus (DENV) is a mosquito-borne flavivirus that causes serious human disease and mortality worldwide. There is no specific antiviral therapy or vaccine for DENV infection. Alterations in gene expression during DENV infection of the mosquito and the impact of these changes on virus infection are important events to investigate in hopes of creating new treatments and vaccines. We previously identified 203 genes that were 5-fold differentially upregulated during flavivirus infection of the mosquito. Here, we examined the impact of silencing 100 of the most highly upregulated gene targets on DENV infection in its mosquito vector. We identified 20 genes that reduced DENV infection by at least 60% when silenced. We focused on one gene, a putative cysteine rich venom protein (SeqID AAEL000379; CRVP379), whose silencing significantly reduced DENV infection in Aedes aegypti cells. Here, we examine the requirement for CRVP379 during DENV infection of the mosquito and investigate the mechanisms surrounding this phenomenon. We also show that blocking CRVP379 protein with either RNAi or specific antisera inhibits DENV infection in Aedes aegypti. This work identifies a novel mosquito gene target for controlling DENV infection in mosquitoes that may also be used to develop broad preventative and therapeutic measures for multiple flaviviruses.

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