Multifaceted contributions of Dicer2 to arbovirus transmission by Aedes aegypti

Arthropod-borne viruses (arboviruses) transmitted by Aedes aegypti mosquitoes 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 in Ae. aegypti is well established, its effective impact on arbovirus transmission is surprisingly poorly understood. Here, we used CRISPR/Cas9-mediated gene editing to create a line of Ae. aegypti in which we mutated Dicer2, a gene encoding the RNA sensor and key component of the siRNA pathway. Our Dicer2 null mutant line is viable and fertile, and only displays minor fitness defects despite being unable to produce siRNAs. The loss of Dicer2 affects 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 that Dicer2 null mutants and wild-type mosquitoes display an overall similar level of vector competence. Additionally, Dicer2 null mutants undergo significant virus-induced mortality during infection with chikungunya virus, but not dengue virus. Together, our results define a multifaceted role for Dicer2 in the transmission of arboviruses by Ae. aegypti mosquitoes and pave the way for further mechanistic investigations.