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Updated: Jul 1, 2025
Effective Oral RNA Interference RNAi Administration to Adult Anopheles gambiae Mosquitoes
Published on: March 1, 2022
Limitations in harnessing oral RNA interference as an antiviral strategy in Aedes aegypti
Ottavia Romoli1, Annabelle Henrion-Lacritick1, Hervé Blanc1
1Institut Pasteur, Université Paris Cité, CNRS UMR3569, Viruses and RNAi Unit, F-75015 Paris, France.
Abstract:
Mosquitoes, particularly Aedes aegypti, are critical vectors for globally significant pathogenic viruses. This study examines the limitations of oral RNA interference (RNAi) as a strategy to disrupt viral transmission by Ae. aegypti. We hypothesized that double-stranded RNA (dsRNA) targeting the Zika virus (ZIKV) or chikungunya virus (CHIKV) genomes produced by engineered bacterial symbionts could trigger an antiviral response. Mosquitoes mono-colonized with Escherichia coli producing dsZIK or dsCHIK did not display reduced viral titers following exposure to virus-contaminated bloodmeals and failed to generate dsZIK- or dsCHIK-derived small interfering RNAs. To address potential limitations of bacterial dsRNA release, we explored dsRNA inoculation via feeding and injection. Although viral replication was impeded in mosquitoes injected with dsZIK or dsCHIK, no antiviral effect was observed in dsRNA-fed mosquitoes. These findings highlight complexities of implementing oral RNAi as an antiviral strategy in Ae. aegypti and warrant further exploration of local and systemic RNAi mechanisms.
Insights
Oral RNA interference (RNAi) using engineered bacteria failed to control Zika and chikungunya viruses in Aedes aegypti mosquitoes. Mosquitoes did not show reduced viral loads after exposure to contaminated bloodmeals.
Area of Science:
- Vector-borne diseases
- Molecular biology
- Entomology
Background:
- Aedes aegypti mosquitoes transmit critical arboviruses like Zika and chikungunya.
- RNA interference (RNAi) is a gene-silencing mechanism with potential for vector control.
- Oral RNAi strategies aim to disrupt pathogen replication within the vector.
Purpose of the Study:
- To evaluate the efficacy of bacterial-produced double-stranded RNA (dsRNA) for controlling Zika virus (ZIKV) and chikungunya virus (CHIKV) in Aedes aegypti.
- To investigate limitations of oral RNAi delivery and systemic antiviral responses in mosquitoes.
Main Methods:
- Engineered Escherichia coli to produce dsRNA targeting ZIKV (dsZIK) or CHIKV (dsCHIK).
- Mono-colonized Ae. aegypti with engineered E. coli and assessed viral titers after infectious bloodmeals.
- Administered dsRNA via feeding and injection to evaluate antiviral effects and small interfering RNA (siRNA) generation.
Main Results:
- Mosquitoes colonized with dsRNA-producing bacteria did not show reduced ZIKV or CHIKV titers.
- No dsRNA-derived siRNAs were detected in mosquitoes exposed to engineered bacteria.
- Direct injection of dsRNA impeded viral replication, but oral feeding of dsRNA had no antiviral effect.
Conclusions:
- Bacterial production and oral delivery of dsRNA are insufficient to induce antiviral RNAi in Ae. aegypti.
- Challenges exist in achieving effective dsRNA uptake and systemic RNAi response via oral routes.
- Further research is needed to understand local and systemic RNAi mechanisms for vector-borne disease control.
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