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, but its effective impact on arbovirus transmission is surprisingly poorly understood. Here, we use CRISPR-Cas9-mediated gene editing in vivo to mutate Dicer2, a gene encoding the RNA sensor and key component of the siRNA pathway. The loss of Dicer2 enhances early viral replication and systemic viral dissemination of four medically significant arboviruses (chikungunya, Mayaro, dengue, and Zika viruses) representing two viral families. However, Dicer2 mutants and wild-type mosquitoes display overall similar levels of vector competence. In addition, Dicer2 mutants undergo significant virus-induced mortality during infection with chikungunya 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. [Display omitted] •Dicer2 limits early replication of chikungunya, Mayaro, dengue, and Zika viruses•Dicer2 hinders systemic viral dissemination of the aforementioned arboviruses•Dicer2 mutants and wild-type mosquitoes display similar levels of vector competence•Dicer2 mutants are sensitive to chikungunya virus, but not to dengue virus infection In this study, Merkling et al. find that genetically disabling the antiviral factor Dicer2 has a limited impact on the ability of the mosquito Aedes aegypti to acquire, replicate, and subsequently transmit medically relevant arboviruses such as chikungunya, Mayaro, dengue, and Zika viruses.