Université de Lyon, Lyon, France.
Autophagy. 2012 Jul 1;8(7):1136-7. doi: 10.4161/auto.20339. Epub 2012 Jun 22.
Several intracellular pathogens have the ability to avoid or exploit the otherwise destructive process of autophagy. RNA viruses are constantly confronted with cellular autophagy, and several of them hijack autophagy during the infectious cycle to improve their own replication. Nevertheless, our knowledge of viral molecular strategies used to manipulate autophagy remains limited. Our study allowed the identification of molecular interactions between 44 autophagy-associated proteins and 83 viral proteins belonging to five different RNA virus families. This interactome revealed that the autophagy network machinery is highly targeted by RNA viruses. Interestingly, whereas some autophagy-associated proteins are targeted by only one RNA virus family, others are recurrent targets of several families. Among them, we found IRGM as the most targeted autophagy-associated protein. Downregulation of IRGM expression prevents autophagy induction by measles virus, HCV and HIV-1, and compromises viral replication. Our work combined interactomic and analytical approaches to identify potential pathogen virulence factors targeting autophagy.
几种细胞内病原体具有逃避或利用自噬这一原本具有破坏性的过程的能力。RNA 病毒经常会遇到细胞自噬，其中一些病毒会在感染周期中劫持自噬来提高自身的复制能力。然而，我们对于病毒分子策略用于操纵自噬的了解仍然有限。我们的研究鉴定了 44 种与自噬相关的蛋白和 83 种属于五个不同 RNA 病毒科的病毒蛋白之间的分子相互作用。该相互作用组揭示了自噬网络机制是 RNA 病毒的高度靶向目标。有趣的是，尽管一些与自噬相关的蛋白仅被一种 RNA 病毒家族靶向，而其他蛋白则是多个家族的反复靶向目标。其中，我们发现 IRGM 是最受靶向的与自噬相关的蛋白。下调 IRGM 的表达可防止麻疹病毒、丙型肝炎病毒和 HIV-1 诱导自噬，并损害病毒复制。我们的工作结合了相互作用组学和分析方法，以鉴定针对自噬的潜在病原体毒力因子。
