The role of mosquito NF-κB-mediated innate immunity in controlling vector-borne virus transmission and emergence

Despite their evolutionary divergence, insects share many (but not all) immune responses with humans and other vertebrates. Many major breakthroughs in the field of immunology were first made or built upon in insects, particularly the fruit fly Drosophila melanogaster. There is a renewed and growing interest in expanding our understanding of insect immunology beyond model organisms to economically important livestock (e.g. honeybees, silkworms) and pests (e.g. aphids), disease vectors of public health and veterinary importance (e.g. mosquitoes), and species exploited as biotechnology platforms (e.g. moth-derived protein expression systems). This talk will explore the role of NF-κB-mediated innate immunity in controlling the replication and transmission of vector-borne viruses by the invasive globally distributed tropical mosquito species Aedes aegypti. We were the first to gene edit mosquito cells using the CRISPR-Cas9 system, and developed novel ankyrons to validate our gene knockouts of NF-κB family transcription factors. Using these new tools, we have shown that NF-κB-dependent immune signalling poses an important barrier to vector-borne virus replication and species jumping. These findings pave the way for developing novel genetically modified mosquitoes refractory to vector-borne disease transmission to reduce the global public health burden of these increasingly important diseases.