# Identification of candidate genes conditioning mosquito immune response to arboviruses

> **NIH NIH R21** · UNIVERSITY OF NOTRE DAME · 2020 · $193,250

## Abstract

PROJECT ABSTRACT
 Dengue virus (DENV) occurs as 4 serotypes that are biologically transmitted between humans
principally by Aedes aegypti mosquitoes. This virus causes dengue fever, which is the most widespread and
significant arboviral disease in the world. It also is the etiological agent of dengue hemorrhagic fever (DHF)
and dengue shock syndrome (DSS), severe and sometimes fatal forms of the disease. At present, mosquito
control remains the only option for preventing transmission to humans of dengue and several other
arboviruses. A. aegypti is also a primary vector for Zika and chikungunya virus as well as yellow fever virus in
urban areas, throughout the tropics and subtropics, and is a recognized model for innate immunity studies with
both protozoan (malaria: Plasmodium gallinaceum) and metazoan (lymphatic filariasis: Brugia malayi) parasite
infections. The long-term goals of this research are to identify, isolate, and characterize genetic factors
conditioning the A. aegypti innate immune response to arbovirus infection. Our general hypothesis is that a
very small number of key genes condition a susceptible or refractory innate immune response to DENV and
likely to ZIKV and other pathogens as well. Our rationale for this research is that these genes once identified
could provide a foundation to explore development of a next generation of targeted and effective genetic
control strategies. Our project builds on extensive preliminary data as well as the existing whole genome
assembly for A. aegypti. The project specific aim is designed to employ well-established methods to identify
discrete genome regions defined as quantitative trait loci (QTL) containing key genes that condition arbovirus
susceptibility and identify all genes within these regions for future targeted functional analysis. The proposed
research is significant as we expect it to better inform our basic understanding of the innate immune system in
A. aegypti, with an overarching goal to facilitate development of new genetic control paradigms. Our proposed
research is innovative because for the first time, it will integrate genetic, genomic, and phenotypic information
on the A. aegypti innate immune response to DENV and ZIKV infection as derived from well-characterized
susceptible and refractory genetic stocks. We expect that knowledge gained in this R21 proposal will provide
critical preliminary data to support future detailed research that has potential to significantly enhance our
understanding of the fundamental innate immune responses that promote or prevent successful arbovirus
infection in this critical vector species, and could provide a model for conducting similar research in other
arthropod/pathogen relationships.

## Key facts

- **NIH application ID:** 9857549
- **Project number:** 5R21AI144095-02
- **Recipient organization:** UNIVERSITY OF NOTRE DAME
- **Principal Investigator:** DAVID W SEVERSON
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $193,250
- **Award type:** 5
- **Project period:** 2019-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9857549

## Citation

> US National Institutes of Health, RePORTER application 9857549, Identification of candidate genes conditioning mosquito immune response to arboviruses (5R21AI144095-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9857549. Licensed CC0.

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