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.

内源性病毒元件 (EVE) 是整合到宿主基因组中的病毒序列。最近在伊蚊基因组中检测到大量非逆转录病毒 EVE ，导致蚊子 EVE 可能控制密切相关病毒的外源感染的假设。在这里，我们通过实验研究了在埃及伊蚊种群中自然发现的 EVE 的作用，该 EVE源自广泛的昆虫特异性病毒细胞融合剂病毒 (CFAV)。使用 CRISPR-Cas9 基因组编辑，我们创建了一个Ae。埃及缺少 CFAV EVE 的线路。EVE 的缺失导致卵巢中 CFAV 复制增加，可能调节病毒的垂直传播。病毒复制是通过 EVE 衍生的 P 元件诱导的懦弱睾丸相互作用 RNA (piRNA) 靶向病毒 RNA 来控制的。我们的研究结果证明，抗病毒 piRNA 是在天然存在的 EVE 及其同源病毒存在的情况下产生的，证明了非逆转录病毒 EVE 与天然昆虫-病毒相互作用中的抗病毒免疫之间的功能联系。