One Sentence Summary:Here we describe the generation of Ae. aegypti mosquitoes that are engineered to confer reduced vector competence to Zika virus (ZIKV) and we discuss how such engineering approach can be used to combat the major health burden of ZIKV and potentially other arboviruses in the future.
Abstract: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 microRNAs (miRNAs) targeting ZIKV is expressed and fully processed following a blood meal in Ae. aegypti , ensuring the formation of mature synthetic miRNAs 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.
MainSince being introduced into the Americas, ZIKV -a mosquito-borne flavivirus -has spread rapidly, causing hundreds of thousands of cases of ZIKV infection 1 . Although most cases remain asymptomatic, infection during pregnancy has been associated with severe congenital abnormalities and pregnancy loss, presenting an unprecedented health threat with long-term consequences 2 . This prompted the World Health Organization to declare ZIKV a Public Health Emergency of International Concern in 2016 1,2 . Currently, there are no clinically approved vaccines to prevent ZIKV and no effective treatment options for infected individuals; thus, vector control remains essential in curtailing the ZIKV epidemic. Like dengue virus (DENV) and chikungunya virus (CHIKV), ZIKV is transmitted primarily by Aedes mosquitoes, which are expanding their habitable range due to urbanization, climate change, and global trade 3 . Current methods of vector control, including removal of standing water and use of insecticides, have not been entirely effective in the fight against the spread of Aedes mosquitoes 3 . Therefore, new game-changing innovative vector control strategies, including those utilizing genetically engineered mosquitoes 4 , are urgently needed to combat the spread of ZIKV and other Aedes -vectored diseases worldwide.Employment of genetically modified (or otherwise altered) insects to manipulate disease-vectoring populations was first proposed decades ago 5 , and due in part to enabling technological advances, has garnered increased interest in recent years 4 . In fact, several strategies for genetic-based vector contr...