Multifaceted contributions ofDicer2to arbovirus transmission byAedes aegypti

AbstractArthropod-borne viruses (arboviruses) transmitted byAedes aegyptimosquitoes are an increasing threat to global health. The small interfering RNA (siRNA) pathway is considered the main antiviral immune pathway of insects, and thus represents a potential key target in the development of novel transmission-blocking strategies against arboviruses. Although the antiviral function of the siRNA pathway inAe. aegyptiis well established, its effective impact on arbovirus transmission is surprisingly poorly understood. Here, we used CRISPR/Cas9-mediated gene editing to create a line ofAe. aegyptiin which we mutatedDicer2, a gene encoding the RNA sensor and key component of the siRNA pathway. OurDicer2null mutant line is viable and fertile, and only displays minor fitness defects despite being unable to produce siRNAs. The loss ofDicer2affects early viral replication and systemic viral dissemination of four medically significant arboviruses (chikungunya, Mayaro, dengue, and Zika viruses) representing two viral families. However, measures of virus transmission potential indicate thatDicer2null mutants and wild-type mosquitoes display an overall similar level of vector competence. Additionally,Dicer2null mutants undergo significant virus-induced mortality during infection with chikungunya virus, but not dengue virus. Together, our results define a multifaceted role forDicer2in the transmission of arboviruses byAe. aegyptimosquitoes and pave the way for further mechanistic investigations.