Dengue virus infection of Aedes aegypti requires a putative cysteine rich venom protein
Autor(es): Londono-Renteria, Berlin; Troupin, Andrea; Conway, Michael J.; Vesely, Diana; Ledizet, Michael; Roundy, Christopher M.; Cloherty, Erin; Jameson, Samuel; Vanlandingham, Dana; Higgs, Stephen
Resumo: 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 greater than or equal to 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.
Palavras-Chave: Human diseases; Cysteine; Disease control; Pest control; Pathogens; Vaccines; Aquatic insects; Ecosystem disturbance; Public health; Gene expression; Mortality; Antisera; RNA-mediated interference; Venom; Infection; Dengue; Proteins; Dengue virus; Aedes aegypti; Flavivirus
Imprenta: Plos Pathogens, v. 11, n. 10, 2015.
Descritores: Aedes aegypti - Cell ; Aedes aegypti - Proteins ; Aedes aegypti - RNA ; Aedes aegypti - Virus ; Aedes aegypti - Vaccine ; Aedes aegypti - Dengue ; Aedes aegypti - Public health
Data de publicação: 2015