Dengue Virus Infection of Aedes aegypti Requires a Putative Cysteine Rich Venom Protein.
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.
Department of Pathology, Microbiology & Immunology, University of South Carolina School of Medicine, Columbia, South Carolina, United States of America.
Berlin
B
Londono-Renteria
Department of Pathology, Microbiology & Immunology, University of South Carolina School of Medicine, Columbia, South Carolina, United States of America.
Andrea
A
Troupin
Foundational Sciences, Central Michigan University College of Medicine, Mount Pleasant, Michigan, United States of America.
Michael J
MJ
Conway
L2 Diagnostics, New Haven, Connecticut, United States of America.
Diana
D
Vesely
L2 Diagnostics, New Haven, Connecticut, United States of America.
Michael
M
Ledizet
Department of Tropical Medicine, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, United States of America.
Christopher M
CM
Roundy
Department of Tropical Medicine, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, United States of America.
Erin
E
Cloherty
Department of Tropical Medicine, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, United States of America.
Samuel
S
Jameson
Biosecurity Research Institute, Kansas State University, Manhattan, Kansas, United States of America; Diagnostic Medicine and Pathobiology, Kansas State University, Manhattan, Kansas, United States of America.
Dana
D
Vanlandingham
Biosecurity Research Institute, Kansas State University, Manhattan, Kansas, United States of America; Diagnostic Medicine and Pathobiology, Kansas State University, Manhattan, Kansas, United States of America.
Stephen
S
Higgs
Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America; Howard Hughes Medical Institute, Chevy Chase, Maryland, United States of America.
Erol
E
Fikrig
Department of Pathology, Microbiology & Immunology, University of South Carolina School of Medicine, Columbia, South Carolina, United States of America.
Tonya M
TM
Colpitts
D000330:Aedes / Q000821:virology*; D000818:Animals; D001180:Arthropod Venoms / Q000378:metabolism; D015153:Blotting, Western; D003545:Cysteine; D003715:Dengue / Q000378:metabolism*; D003716:Dengue Virus / Q000472:pathogenicity*; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D020868:Gene Silencing; D019476:Insect Proteins / Q000378:metabolism*; D007303:Insect Vectors / Q000378:metabolism / Q000821:virology*; D016133:Polymerase Chain Reaction; D034741:RNA, Small Interfering; D014162:Transfection
D001180:Arthropod Venoms; D019476:Insect Proteins; D034741:RNA, Small Interfering; D003545:Cysteine