Non-retroviral Endogenous Viral Element Limits Cognate Virus Replication in Aedes aegypti Ovaries

Endogenous viral elements (EVEs) are viral sequences integrated in host genomes. A large number of non-retroviral EVEs was recently detected in Aedes mosquito genomes, leading to the hypothesis that mosquito EVEs may control exogenous infections by closely related viruses. Here, we experimentally investigated the role of an EVE naturally found in Aedes aegypti populations and derived from the widespread insect-specific virus, cell-fusing agent virus (CFAV). Using CRISPR-Cas9 genome editing, we created an Ae. aegypti line lacking the CFAV EVE. Absence of the EVE resulted in increased CFAV replication in ovaries, possibly modulating vertical transmission of the virus. Viral replication was controlled by targeting of viral RNA by EVE-derived P-element-induced wimpy testis-interacting RNAs (piRNAs). Our results provide evidence that antiviral piRNAs are produced in the presence of a naturally occurring EVE and its cognate virus, demonstrating a functional link between non-retroviral EVEs and antiviral immunity in a natural insect-virus interaction. [Display omitted] •Aedes aegypti harbors EVEs with high sequence identity to a contemporary RNA virus•EVE-derived piRNAs target genomic viral RNA in infected mosquitoes•Ablation of EVE results in increased viral replication in Aedes aegypti ovaries•piRNA pathway fulfills antiviral function in presence of EVE and cognate virus Suzuki, Baidaliuk et al. identify a new endogenous viral element (EVE) in the genome of Aedes aegypti mosquitoes that was derived from a currently circulating, insect-specific flavivirus. Using this naturally occurring interaction, they demonstrate that a non-retroviral EVE confers antiviral immunity against its cognate virus via the piRNA pathway.