Reduced insulin/IGF-1 signalling (rIIS) improves survival across diverse taxa and there is a growing interest in its role in regulating immune function. Whilst rIIS can improve anti-bacterial resistance, the consequences for anti-viral immunity are yet to be systematically examined. Here, we show that rIIS in adult Caenorhabditis elegans increases the expression of key genes in two different anti-viral immunity pathways, whilst reducing viral load in old age, increasing survival and reducing rate-of-senescence under infection by naturally occurring positive-sense single-stranded RNA Orsay virus. We found that both drh-1 in the anti-viral RNA interference (RNAi) pathway and cde-1 in the terminal uridylation-based degradation of viral RNA pathway were upregulated in early adulthood under rIIS and increased anti-viral resistance was not associated with reproductive costs. Remarkably, rIIS increased anti-viral gene expression only in infected worms, potentially to curb the costs of constitutively upregulated immunity. RNA viruses are found across taxa from plants to mammals and we demonstrate a novel role for rIIS in regulating resistance to viral infection. We therefore highlight this evolutionarily conserved signalling pathway as a promising therapeutic target to improve anti-viral immunity.

减少胰岛素/IGF-1 信号 (rIIS) 可改善不同类群的存活率，并且人们对其在调节免疫功能中的作用越来越感兴趣。虽然 rIIS 可以提高抗菌耐药性，但其对抗病毒免疫的影响仍有待系统研究。在这里，我们发现成年秀丽隐杆线虫中的 rIIS增加了两种不同抗病毒免疫途径中关键基因的表达，同时减少了老年时的病毒载量，通过自然发生的正向感染提高了存活率并降低了衰老率单链RNA奥赛病毒。我们发现，在 rIIS 的成年早期，抗病毒 RNA 干扰（RNAi）途径中的drh-1和病毒 RNA 末端尿苷化降解途径中的cde-1均上调，并且抗病毒耐药性的增加与繁殖成本。值得注意的是，rIIS 仅在受感染的蠕虫中增加抗病毒基因表达，这可能会抑制组成性上调免疫的成本。 RNA 病毒存在于从植物到哺乳动物的各种分类群中，我们证明了 rIIS 在调节病毒感染抵抗力方面的新作用。因此，我们强调这种进化上保守的信号通路作为改善抗病毒免疫力的有前途的治疗靶点。