New Targets for Reproductive Control of Mosquito Vectors Project summary/abstract In this project, we will investigate the male seminal fluid proteins (SFPs) of a major disease vector of dengue, Zika and chikungunya viruses: the yellow fever mosquito (Aedes aegypti). Insect SFPs trigger major changes in female physiology, conducive to high fertility (e.g. increased egg production), regulating re-mating and, in mosquitoes, potentially regulating blood feeding physiology. Dengue is an old scourge, but new pathogens such as chikungunya and Zika that cycled silently in their sylvatic backdrop have surged forward and crossed hemispheres with a vengeance. There is an immediate need to develop novel and effective vector control strategies for these vectors. In the present funding period, we identified Aedes SFPs and obtained bioactive fractions and identified components. We developed assays for testing the effects of the components, and have been successful in using CRISPR-based genome editing to mutate our first candidates for bioactive SFPs. We also determined the effect of mating on SFP stores (and production) in males, and on the transcriptome of the mated female. In this renewal application, for continued support for this project, we propose three specific aims to (1) identify and functionally characterize bioactive SFPs in vivo in Ae. aegypti, (2) determine female molecular responses to SFPs in general and physiological and molecular responses to specific, bioactive, SFPs and (3) understand the phenotypic and genetic variation of SFPs and their responsive targets in field relevant populations of this mosquito vector. Our goal is to identify SFPs, and SFP targets, that could be manipulated as a novel means of reproductive control, or to modify the blood feeding physiology of these insects that transmit deadly pathogens, with the long-term goal to reduce or eliminate virus transmission to people.

Public Health Relevance

To reduce or eliminate transmission of serious viruses causing dengue, Zika, and chikungunya, methods are needed to control the reproductive capacity, or blood feeding physiology, of the mosquitoes that transmit them. Seminal fluid proteins that modulate mosquito mating, egg production, survival or blood feeding physiology, and the female genes that respond to these proteins, are excellent species-specific targets for such vector control. Having identified fractions of Aedes seminal proteins with bioactivity, as well as post-mating transcriptome changes in Aedes aegypti females, we will now pinpoint the specific seminal proteins that regulate female post-mating physiology, the genes that respond to them, and the natural variation of these potential vector-control targets in field- caught mosquitoes from virus endemic settings.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Vector Biology Study Section (VB)
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Costero-Saint Denis, Adriana
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Cornell University
Earth Sciences/Resources
United States
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Degner, Ethan C; Ahmed-Braimah, Yasir H; Borziak, Kirill et al. (2018) Proteins, transcripts, and genetic architecture of seminal fluid and sperm in the mosquito Aedes aegypti. Mol Cell Proteomics :
Hatala, A J; Harrington, L C; Degner, E C (2018) Age and Body Size Influence Sperm Quantity in Male Aedes albopictus (Diptera: Culicidae) Mosquitoes. J Med Entomol 55:1051-1054
Villarreal, Susan M; Pitcher, Sylvie; Helinski, Michelle E H et al. (2018) Male contributions during mating increase female survival in the disease vector mosquito Aedes aegypti. J Insect Physiol 108:1-9
Sánchez-Vargas, Irma; Harrington, Laura C; Doty, Jeffrey B et al. (2018) Demonstration of efficient vertical and venereal transmission of dengue virus type-2 in a genetically diverse laboratory strain of Aedes aegypti. PLoS Negl Trop Dis 12:e0006754
Degner, Ethan C; Harrington, Laura C (2016) Polyandry Depends on Postmating Time Interval in the Dengue Vector Aedes aegypti. Am J Trop Med Hyg 94:780-5
Degner, Ethan C; Harrington, Laura C (2016) A mosquito sperm's journey from male ejaculate to egg: Mechanisms, molecules, and methods for exploration. Mol Reprod Dev 83:897-911
Alfonso-Parra, Catalina; Ahmed-Braimah, Yasir H; Degner, Ethan C et al. (2016) Mating-Induced Transcriptome Changes in the Reproductive Tract of Female Aedes aegypti. PLoS Negl Trop Dis 10:e0004451
Sirot, Laura K; Wong, Alex; Chapman, Tracey et al. (2014) Sexual conflict and seminal fluid proteins: a dynamic landscape of sexual interactions. Cold Spring Harb Perspect Biol 7:a017533
Alfonso-Parra, Catalina; Avila, Frank W; Deewatthanawong, Prasit et al. (2014) Synthesis, depletion and cell-type expression of a protein from the male accessory glands of the dengue vector mosquito Aedes aegypti. J Insect Physiol 70:117-24
Boes, Kathryn E; Ribeiro, José M C; Wong, Alex et al. (2014) Identification and characterization of seminal fluid proteins in the Asian tiger mosquito, Aedes albopictus. PLoS Negl Trop Dis 8:e2946

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