Institute of Biochemistry and Molecular Biology, Faculty of Medicine, RWTH Aachen University, Pauwelsstraße 30, 52074, Aachen, Germany.
Cell Mol Life Sci. 2022 May 10;79(6):288. doi: 10.1007/s00018-022-04290-6.
The innate immune system, the primary defense mechanism of higher organisms against pathogens including viruses, senses pathogen-associated molecular patterns (PAMPs). In response to PAMPs, interferons (IFNs) are produced, allowing the host to react swiftly to viral infection. In turn the expression of IFN-stimulated genes (ISGs) is induced. Their products disseminate the antiviral response. Among the ISGs conserved in many species are those encoding mono-ADP-ribosyltransferases (mono-ARTs). This prompts the question whether, and if so how, mono-ADP-ribosylation affects viral propagation. Emerging evidence demonstrates that some mono-ADP-ribosyltransferases function as PAMP receptors and modify both host and viral proteins relevant for viral replication. Support for mono-ADP-ribosylation in virus-host interaction stems from the findings that some viruses encode mono-ADP-ribosylhydrolases, which antagonize cellular mono-ARTs. We summarize and discuss the evidence linking mono-ADP-ribosylation and the enzymes relevant to catalyze this reversible modification with the innate immune response as part of the arms race between host and viruses.
先天免疫系统是高等生物抵御包括病毒在内的病原体的主要防御机制，它可以感知病原体相关的分子模式 (PAMPs)。针对 PAMPs，干扰素 (IFNs) 会被产生，使宿主能够迅速对病毒感染做出反应。反过来，干扰素刺激基因 (ISGs) 的表达也会被诱导。它们的产物会传播抗病毒反应。在许多物种中保守的 ISGs 中，有那些编码单 ADP-核糖基转移酶 (mono-ARTs) 的基因。这就引发了一个问题，即单 ADP-核糖基化是否以及如何影响病毒的繁殖。新出现的证据表明，一些单 ADP-核糖基转移酶作为 PAMP 受体发挥作用，修饰与病毒复制相关的宿主和病毒蛋白。单 ADP-核糖基化在病毒-宿主相互作用中的作用得到了支持，因为一些病毒编码单 ADP-核糖基水解酶，它们可以拮抗细胞内的单 ADP-核糖基转移酶。我们总结并讨论了将单 ADP-核糖基化与相关酶联系起来的证据，这些酶与先天免疫反应中作为宿主和病毒之间军备竞赛的一部分的可逆修饰有关。
