# Aedes antiviral RNAi pathway

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2021 · $762,720

## Abstract

SUMMARY
 Arboviruses remain an immense public health threat, causing yearly large epidemics. The overarching aim
of this research is to better understand the role of the Aedes aegypti RNA interference (RNAi) pathway in
antiviral defense and innate immunity, and to generate knowledge and tools for the development of new
methods to control arbovirus transmission. Population replacement of wild-type with genetically modified
mosquitoes incapable of pathogen transmission is emerging as a promising complement to other disease
control methods. Because Ae. aegypti transmits multiple arbovirus pathogens that are frequently sympatric, it
is important for a transgenic mosquito to be resistant to multiple pathogens. The siRNA pathway-mediated
antiviral defense system is known to act against a broad range of viruses. However, despite the RNAi
pathway's emergence as the major pan-antiviral defense system it remains understudied in mosquitoes. Our
research plan is designed to test the overarching hypothesis that the A. aegypti proteins, Dicer-2 (Dcr-2), R2D2
and Argonaute-2 (Ago-2), are key components mediating an RNA silencing response that is broadly protective
against arbovirus infections. We will use of siRNA-deficient loss-of-function mutants and transgenic
mosquitoes over-expressing Dcr-2, Ago-2 and R2D2 that will be generated in Aim 1. With these genetic tools
we will clarify the temporal and spatial specificity of the antiviral response in Aim 2, and investigate possible
inter-tissue signaling and regulation of vertical transmission in Aim 3. In Aim 4 we will address interactions
between the RNAi pathway and other innate immunity defense systems. This project utilizes the
complementary expertise of Drs Dimopoulos and Myles with the arbovirus infection systems, mosquito
transgenesis, mosquito innate immunity and RNAi/small RNA biology. Our proposed project will also generate
powerful tools for studying other aspects of the RNAi pathway in Ae. aegypti biology.

## Key facts

- **NIH application ID:** 10054161
- **Project number:** 5R01AI141532-03
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** George Dimopoulos
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $762,720
- **Award type:** 5
- **Project period:** 2018-11-20 → 2023-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10054161

## Citation

> US National Institutes of Health, RePORTER application 10054161, Aedes antiviral RNAi pathway (5R01AI141532-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10054161. Licensed CC0.

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