A Zika virus-responsive sensor-effector system inAedes aegypti

Abstract

Zika virus (ZIKV) is a recently re-emerged flavivirus transmitted primarily through the bite of an infected mosquito, Aedes aegypti being the main vector. ZIKV infection is associated with a range of adverse effects; infection during pregnancy can lead to foetal abnormalities, including microcephaly. Lacking a licensed vaccine, or specific therapeutics, control of ZIKV transmission focuses on vector control. However, in most transmission settings, current methods are insufficient to successfully control ZIKV, or other similarly-transmitted arboviruses such as dengue and chikungunya viruses. This has stimulated interest in genetics-based methods, either to reduce the number of mosquitoes (population suppression), or to make mosquitoes less able to transmit (population modification). Here, we describe a method to selectively eliminate infected mosquitoes, using a virus sensor inserted into the mosquito genome and coupled to a quorum-counting lethal effector. In mosquitoes, ZIKV normally establishes persistent, lifelong infection; survival of these infected mosquitoes is crucial to transmission potential. Correspondingly, removal of infected mosquitoes can reduce vectorial capacity of a mosquito population, i.e. ability to transmit. Since relatively few mosquitoes become infected, typically <2%, engineered hypersensitivity to ZIKV would have only a modest population-level fitness cost, and lower still if transmission were successfully reduced by such means.

Manipulating the Destiny of Wild Populations Using CRISPR

“…A number of effector strategies have been developed in mosquitoes, including RNA interference (28,85,86,145,156,195,237), single-chain antibodies (29,69,238), peptides (116,163,239), toxic proteins (19), and upregulation of immune factors (77). Recently, CRISPR has expanded this toolbox to include antiviral effector development.…”

CRISPR-based gene drives generate super-Mendelian inheritance in the disease vectorCulex quinquefasciatus

“…aegypti, then functional modification drives in this species will also require the development of disease-refractory systems, as have been developed for some pathogens in Ae. aegypti [36][37][38][39] . With transgenic manipulation of Cx.…”

CRISPR-based gene drives generate super-Mendelian inheritance in the disease vector Culex quinquefasciatus.

“…aegypti, then functional modi cation drives in this species will also require the development of disease-refractory systems, as have been developed for some pathogens in Ae. aegypti [36][37][38][39] . With transgenic manipulation of Cx.…”