Antiviral immunity in insects is mediated by the RNA interference (RNAi) pathway. Viruses evade antiviral RNAi by expressing virulence factors known as viral suppressors of RNAi (VSR). Here, we report the identification of VINR, a Drosophila VSR-interacting long non-coding (lnc) RNA that activates non-canonical innate immune signaling upon detection of the dsRNA-binding VSR of Drosophila C virus (DCV). VINR is required for the induction of antimicrobial peptide (AMP) genes but dispensable for antiviral RNAi. VINR functions by preventing the ubiquitin proteasome-dependent degradation of Cactin, a coiled-coil and arginine-serine-rich domain-containing protein that regulates a non-cannonical antimicrobial pathway for AMP induction. CRISPR-Cas9 knockout of VINR in Drosophila cells enhances DCV replication independently of antiviral RNAi, and VINR-knockout adult flies exhibit enhanced disease susceptibility to DCV and bacteria. Our findings reveal a counter counter-defense strategy activated by a lncRNA in response to the viral suppression of the primary antiviral RNAi immunity.

中文翻译：

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RNAi病毒抑制剂的lncRNA感应激活果蝇中的非经典先天免疫信号。

昆虫的抗病毒免疫是通过RNA干扰（RNAi）途径介导的。病毒通过表达被称为RNAi病毒抑制剂（VSR）的毒性因子来逃避抗病毒RNAi。在这里，我们报告鉴定VINR，果蝇与VSR相互作用的长非编码（lnc）RNA，该蛋白在检测到果蝇C病毒（DCV）的dsRNA结合VSR后激活非规范的先天免疫信号。VINR是诱导抗菌肽（AMP）基因所必需的，但对于抗病毒RNAi则是必需的。VINR通过阻止仙人掌素的泛素蛋白酶体依赖性降解而发挥作用，该蛋白质是卷曲螺旋和富含精氨酸丝氨酸的结构域蛋白，可调节AMP诱导的非规范性抗菌途径。果蝇细胞中VINR的CRISPR-Cas9敲除可独立于抗病毒RNAi增强DCV复制，VINR基因敲除的成年苍蝇对DCV和细菌的疾病易感性增强。我们的发现揭示了由lncRNA激活的反防御策略，以响应病毒对主要抗病毒RNAi免疫的抑制。