Journal Article

Engineered resistance to Zika virus in transgenic Aedes aegypti expressing a polycistronic cluster of synthetic small RNAs

Paradkar, Prasad N., Akbari, Omar S., Klein, Melissa J., Li, Ming, Antoshechkin, Igor, Li, Hsing-Han, Chen, Chun-Hong, Gamez, Stephanie, Wang, Hsin-Wei, Duchemin, Jean-Bernard, Buchman, Anna

2019

Overview

Recent Zika virus (ZIKV) outbreaks have highlighted the necessity for development of novel vector control strategies to combat arboviral transmission, including genetic versions of the sterile insect technique, artificial infection with Wolbachia to reduce population size and/or vectoring competency, and gene drive-based methods. Here, we describe the development of mosquitoes synthetically engineered to impede vector competence to ZIKV. We demonstrate that a polycistronic cluster of engineered synthetic small RNAs targeting ZIKV is expressed and fully processed in Aedes aegypti, ensuring the formation of mature synthetic small RNAs in the midgut where ZIKV resides in the early stages of infection. Critically, we demonstrate that engineered Ae. aegypti mosquitoes harboring the anti-ZIKV transgene have significantly reduced viral infection, dissemination, and transmission rates of ZIKV. Taken together, these compelling results provide a promising path forward for development of effective genetic-based ZIKV control strategies, which could potentially be extended to curtail other arboviruses.

• Publisher: National Academy of Sciences
• Subject: Aedes aegypti / Animal biology / Animals / Animals, Genetically Modified / Animals, Genetically Modified - genetics / Animals, Genetically Modified - virology / Aquatic insects / Bacteria / Biological Sciences / Clusters / Culicidae / Directional control / Disease Outbreaks / Disease resistance / Ecology, environment / Genetics / Health / Humans / Infections / Insects / Invertebrate Zoology / Life Sciences / Microbiology and Parasitology / Midgut / Mosquito Vectors / Mosquito Vectors - genetics / Mosquito Vectors - virology / Mosquitoes / Outbreaks / Parasitology / Pest control / Pest outbreaks / Population number / Saliva / Saliva - virology / Sterilized organisms / Vector-borne diseases / Viral infections / Viral Load / Viral Load - genetics / Virology / Viruses / Wolbachia / Wolbachia - pathogenicity / Wolbachia - virology / Zika Virus / Zika Virus - genetics / Zika Virus - pathogenicity / Zika Virus Infection / Zika Virus Infection - genetics / Zika Virus Infection - transmission / Zika Virus Infection - virology