Abstract
SummaryEndogenous 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.
Highlights
Host genomes often harbor fragments of viral genomes, referred to as endogenous viral elements (EVEs), that are inherited as host alleles [1]
We identified several potential Endogenous viral elements (EVEs) structures based on samples for which reads aligned only to segments of the cell-fusing agent virus (CFAV) genome, in addition to samples for which reads covered the entire CFAV genome, presumably representing true CFAV infections (Data S1)
CFAV-EVEs Produce P-element-induced wimpy testis-interacting RNAs (piRNAs) that Interact with Viral RNA from a Natural CFAV Infection Our outbred Ae. aegypti colony from Thailand is naturally infected with a wild-type strain of CFAV, which we previously isolated and named CFAV-KPP [32]
Summary
Host genomes often harbor fragments of viral genomes, referred to as endogenous viral elements (EVEs), that are inherited as host alleles [1]. The best-studied EVEs are derived from mammalian retroviruses, which actively integrate their viral DNA into the host genome during their replication cycle. Retroviral EVEs play important roles in host physiology and antiviral immunity [2]. Recent bioinformatic surveys identified non-retroviral EVEs in a wide range of animal genomes, albeit their function was only studied in cell lines or protozoa [3,4,5,6,7,8,9,10,11]. The endogenization of non-retroviral sequences is presumably mediated by the activity of transposable elements (TEs), which are mobile DNA sequences ubiquitously found in eukaryotic genomes. The reverse transcription activity of retrotransposons is the likely mechanism generating non-retroviral DNA from RNA viruses, which are the hypothetical precursors of non-retroviral EVEs [15]
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