All viruses with positive-sense RNA genomes replicate on membranous structures in the cytoplasm called replication complexes (RCs). RCs provide an advantageous microenvironment for viral replication, but it is unknown how the host immune system counteracts these structures. Here we show that interferon-gamma (IFNG) disrupts the RC of murine norovirus (MNV) via evolutionarily conserved autophagy proteins and the induction of IFN-inducible GTPases, which are known to destroy the membrane of vacuoles containing bacteria, protists, or fungi. The MNV RC was marked by the microtubule-associated-protein-1-light-chain-3 (LC3) conjugation system of autophagy and then targeted by immunity-related GTPases (IRGs) and guanylate-binding proteins (GBPs) upon their induction by IFNG. Further, the LC3 conjugation system and the IFN-inducible GTPases were necessary to inhibit MNV replication in mice and human cells. These data suggest that viral RCs can be marked and antagonized by a universal immune defense mechanism targeting diverse pathogens replicating in cytosolic membrane structures.

具有正向RNA基因组的所有病毒都在细胞质的膜结构上复制，称为复制复合体（RCs）。RC为病毒复制提供了有利的微环境，但是未知宿主免疫系统如何抵消这些结构。在这里，我们显示干扰素-γ（IFNG）通过进化上保守的自噬蛋白和IFN诱导型GTPases的诱导破坏了鼠诺如病毒（MNV）的RC，已知它们可破坏含有细菌，原生生物或真菌的液泡膜。MNV RC的特征是自噬的微管相关蛋白1-轻链3（LC3）偶联系统，然后在被它们诱导后被免疫相关的GTPases（IRG）和鸟苷结合蛋白（GBP）靶向。干扰素 进一步，为了抑制MNV在小鼠和人类细胞中的复制，LC3偶联系统和IFN诱导型GTPases必不可少。这些数据表明，可以通过针对细胞质膜结构中复制的多种病原体的通用免疫防御机制对病毒RCs进行标记和拮抗。