Diverse mechanisms evolved by DNA viruses to inhibit early host defenses.
Diverse mechanisms evolved by DNA viruses to inhibit early host defenses.
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DOI：
10.1080/10409238.2016.1226250
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发表时间：
2016
影响因子：
6.5
通讯作者：
Cristea IM
中科院分区：
文献类型：
--
作者：
Crow MS;Lum KK;Sheng X;Song B;Cristea IM
在哺乳动物细胞中，对病原体感染的早期防御是通过由免疫调节模式识别受体引导的复杂信号通路网络进行的。作为专性寄生虫，病毒的生存依赖于进化获得的机制，这些机制巧妙地拆除和破坏细胞固有和先天免疫反应。在这里，我们回顾了容纳DNA基因组的病毒能够规避细胞免疫激活的多种机制。我们首先讨论病毒通过转录调控或蛋白质降解对宿主防御蛋白水平的操纵。接下来，我们回顾了通过分子劫持或调节其翻译后修饰状态来重新利用或抑制这些细胞免疫因子的病毒策略。此外，我们探索了感染诱导的细胞凋亡的时间调节，以促进病毒的复制和传播。最后，病毒与宿主的共同进化是通过获得通过病毒模仿宿主因子来抑制宿主防御的优雅机制来强调的。最后，我们提出了一个关于如何描述这些病毒逃避策略的观点，既拓宽了对病毒-宿主相互作用的理解，又揭示了免疫系统在分子水平上的基本功能。这一知识对于理解病毒发病机制的来源，以及设计抗病毒疗法和自身免疫疗法至关重要。
In mammalian cells, early defenses against infection by pathogens are mounted through a complex network of signaling pathways shepherded by immune-modulatory pattern-recognition receptors. As obligate parasites, the survival of viruses is dependent upon the evolutionary acquisition of mechanisms that tactfully dismantle and subvert the cellular intrinsic and innate immune responses. Here, we review the diverse mechanisms by which viruses that accommodate DNA genomes are able to circumvent activation of cellular immunity. We start by discussing viral manipulation of host defense protein levels by either transcriptional regulation or protein degradation. We next review viral strategies used to repurpose or inhibit these cellular immune factors by molecular hijacking or by regulating their post-translational modification status. Additionally, we explore the infection-induced temporal modulation of apoptosis to facilitate viral replication and spread. Lastly, the co-evolution of viruses with their hosts is highlighted by the acquisition of elegant mechanisms for suppressing host defenses via viral mimicry of host factors. In closing, we present a perspective on how characterizing these viral evasion tactics both broadens the understanding of virus-host interactions and reveals essential functions of the immune system at the molecular level. This knowledge is critical in understanding the sources of viral pathogenesis, as well as for the design of antiviral therapeutics and autoimmunity treatments.