Department of Microbiology and Immunology and Center for Pathogen Research, University of Maryland School of Medicine, Baltimore, MD, USA.
Nat Rev Microbiol. 2024 May;22(5):309-321. doi: 10.1038/s41579-023-00995-y. Epub 2023 Dec 15.
Autophagy is a constitutive cellular process of degradation required to maintain homeostasis and turn over spent organelles and aggregated proteins. For some viruses, the process can be antiviral, degrading viral proteins or virions themselves. For many other viruses, the induction of the autophagic process provides a benefit and promotes viral replication. In this Review, we survey the roles that the autophagic pathway plays in the replication of viruses. Most viruses that benefit from autophagic induction block autophagic degradation, which is a 'bend, but don't break' strategy initiating but limiting a potentially antiviral response. In almost all cases, it is other effects of the redirected autophagic machinery that benefit these viruses. This rapid mechanism to generate small double-membraned vesicles can be usurped to shape membranes for viral genome replication and virion maturation. However, data suggest that autophagic maintenance of cellular homeostasis is crucial for the initiation of infection, as viruses have evolved to replicate in normal, healthy cells. Inhibition of autophagic degradation is important once infection has initiated. Although true degradative autophagy is probably a negative for most viruses, initiating nondegradative autophagic membranes benefits a wide variety of viruses.
自噬是一种维持细胞内环境稳定的固有细胞降解过程，用于更新和循环利用老化的细胞器和聚集的蛋白质。对某些病毒而言，自噬过程可以起到抗病毒作用，降解病毒蛋白或病毒本身。而对许多其他病毒而言，自噬的诱导可以促进病毒复制，从而带来益处。在这篇综述中，我们调查了自噬途径在病毒复制中的作用。大多数受益于自噬诱导的病毒会阻止自噬降解，这是一种“曲折但不破裂”的策略，既能启动但又限制潜在的抗病毒反应。在几乎所有情况下，被重新定向的自噬机制的其他作用都有利于这些病毒。这种快速产生双层膜小泡的机制可被病毒劫持用于塑造病毒基因组复制和成熟所需的膜结构。然而，数据表明，自噬对于维持细胞内环境稳态至关重要，因为病毒已经进化到可以在正常、健康的细胞中复制。一旦感染开始，抑制自噬降解就变得很重要。尽管对于大多数病毒而言，真正的降解性自噬可能是负面的，但起始非降解性自噬膜有利于多种病毒。
