Randall Richard E, Goodbourn Stephen
School of Biology, University of St Andrews, The North Haugh, St Andrews KY16 9ST, UK.
Division of Basic Medical Sciences, St George's, University of London, London SW17 0RE, UK.
J Gen Virol. 2008 Jan;89(Pt 1):1-47. doi: 10.1099/vir.0.83391-0.
The interferon (IFN) system is an extremely powerful antiviral response that is capable of controlling most, if not all, virus infections in the absence of adaptive immunity. However, viruses can still replicate and cause disease in vivo, because they have some strategy for at least partially circumventing the IFN response. We reviewed this topic in 2000 [Goodbourn, S., Didcock, L. & Randall, R. E. (2000). J Gen Virol 81, 2341-2364] but, since then, a great deal has been discovered about the molecular mechanisms of the IFN response and how different viruses circumvent it. This information is of fundamental interest, but may also have practical application in the design and manufacture of attenuated virus vaccines and the development of novel antiviral drugs. In the first part of this review, we describe how viruses activate the IFN system, how IFNs induce transcription of their target genes and the mechanism of action of IFN-induced proteins with antiviral action. In the second part, we describe how viruses circumvent the IFN response. Here, we reflect upon possible consequences for both the virus and host of the different strategies that viruses have evolved and discuss whether certain viruses have exploited the IFN response to modulate their life cycle (e.g. to establish and maintain persistent/latent infections), whether perturbation of the IFN response by persistent infections can lead to chronic disease, and the importance of the IFN system as a species barrier to virus infections. Lastly, we briefly describe applied aspects that arise from an increase in our knowledge in this area, including vaccine design and manufacture, the development of novel antiviral drugs and the use of IFN-sensitive oncolytic viruses in the treatment of cancer.
干扰素（IFN）系统是一种极其强大的抗病毒反应，在缺乏适应性免疫的情况下，它能够控制大多数（即便不是全部）病毒感染。然而，病毒仍能在体内复制并引发疾病，因为它们拥有一些策略来至少部分规避IFN反应。我们曾在2000年综述过该主题[古德伯恩，S.，迪德科克，L. & 兰德尔，R. E.（2000年）。《普通病毒学杂志》81卷，2341 - 2364页]，但自那时以来，关于IFN反应的分子机制以及不同病毒如何规避它，已发现了大量信息。这些信息不仅具有根本重要性，还可能在减毒活疫苗的设计与制造以及新型抗病毒药物的研发中具有实际应用价值。在本综述的第一部分，我们描述病毒如何激活IFN系统、IFN如何诱导其靶基因转录以及具有抗病毒作用的IFN诱导蛋白的作用机制。在第二部分，我们描述病毒如何规避IFN反应。在此，我们思考病毒所进化出的不同策略对病毒和宿主可能产生的后果，并讨论某些病毒是否利用IFN反应来调节其生命周期（例如建立和维持持续性/潜伏性感染）、持续性感染对IFN反应的干扰是否会导致慢性疾病，以及IFN系统作为病毒感染的种属屏障的重要性。最后，我们简要描述随着我们在该领域知识的增加而产生的应用方面，包括疫苗设计与制造、新型抗病毒药物的研发以及利用对IFN敏感的溶瘤病毒治疗癌症。
