Mosquito transgenerational antiviral immunity is mediated by vertical transfer of virus DNA sequences and RNAi

Mosquitoes are important vectors for transmission of many viruses of public and veterinary health concern. These viruses most commonly have an RNA genome and infect mosquitoes for life. The principal mosquito antiviral response is the RNAi system which destroys virus RNA. Here, we confirm an earlier study that Aedes aegypti mosquitoes infected with positive-stranded RNA arboviruses can transmit specific immunity to their offspring. We show that this trans-generational immunity requires replication of virus RNA and reverse transcription of vRNA to vDNA in the infected parents and intergenerational transfer of vDNA. This vDNA is both genome-integrated and episomal. The episomal vDNA sequences are flanked by retrotransposon long-terminal repeats, predominantly Copia-like. Integrated vDNA sequences are propagated along several generations but specific immunity is effective only for a few generations and correlates with the presence of vRNA and episomal vDNA. This understanding raises new possibilities for the control of important mosquito-borne virus diseases.