Dengue Virus Infection of Aedes aegypti Requires a Putative Cysteine Rich Venom Protein

PLoS Pathogens

Dana Vanlandingham¹  Erol Fikrig¹  Berlin Londono-Renteria²  Andrea Troupin²  Samuel Jameson³  Christopher M. Roundy³  Erin Cloherty³  Tonya M. Colpitts⁴  Stephen Higgs⁴  Michael J Conway⁵  Diana Vesely⁶  Michael Ledizet⁶ 

[1] Biosecurity Research Institute, Kansas State University, Manhattan, Kansas, United States of America;Department of Pathology, Microbiology & Immunology, University of South Carolina School of Medicine, Columbia, South Carolina, United States of America;Department of Tropical Medicine, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, United States of America;Diagnostic Medicine and Pathobiology, Kansas State University, Manhattan, Kansas, United States of America;Foundational Sciences, Central Michigan University College of Medicine, Mount Pleasant, Michigan, United States of America;L2 Diagnostics, New Haven, Connecticut, United States of America

关键词: Mosquitoes;    Immune serum;    Dengue virus;    Small interfering RNAs;    Antibodies;    RNA interference;    Gene expression;    Aedes aegypti;   

DOI  :  10.1371/journal.ppat.1005202

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY