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在抗病毒治疗和免疫治疗中利用宿主-病毒的进化。

Harnessing host-virus evolution in antiviral therapy and immunotherapy.

作者信息

Heaton Steven M

机构信息

Department of Biochemistry & Molecular Biology Monash University Clayton VIC Australia.

出版信息

Clin Transl Immunology. 2019 Jul 8;8(7):e1067. doi: 10.1002/cti2.1067. eCollection 2019.

Abstract

Pathogen resistance and development costs are major challenges in current approaches to antiviral therapy. The high error rate of RNA synthesis and reverse-transcription confers genome plasticity, enabling the remarkable adaptability of RNA viruses to antiviral intervention. However, this property is coupled to fundamental constraints including limits on the size of information available to manipulate complex hosts into supporting viral replication. Accordingly, RNA viruses employ various means to extract maximum utility from their informationally limited genomes that, correspondingly, may be leveraged for effective host-oriented therapies. Host-oriented approaches are becoming increasingly feasible because of increased availability of bioactive compounds and recent advances in immunotherapy and precision medicine, particularly genome editing, targeted delivery methods and RNAi. In turn, one driving force behind these innovations is the increasingly detailed understanding of evolutionarily diverse host-virus interactions, which is the key concern of an emerging field, neo-virology. This review examines biotechnological solutions to disease and other sustainability issues of our time that leverage the properties of RNA and DNA viruses as developed through co-evolution with their hosts.

摘要

病原体耐药性和研发成本是当前抗病毒治疗方法面临的主要挑战。RNA合成和逆转录的高错误率赋予了基因组可塑性,使RNA病毒能够对抗病毒干预具有显著的适应性。然而,这一特性与一些基本限制相关联,包括可用于操纵复杂宿主以支持病毒复制的信息大小的限制。因此,RNA病毒采用各种方法从其信息有限的基因组中获取最大效用,相应地,这些方法可用于有效的以宿主为导向的治疗。由于生物活性化合物的可用性增加以及免疫疗法和精准医学(特别是基因组编辑、靶向递送方法和RNA干扰)的最新进展,以宿主为导向的方法正变得越来越可行。反过来,这些创新背后的一个驱动力是对进化上不同的宿主-病毒相互作用的理解越来越详细,这是一个新兴领域——新病毒学的关键关注点。本综述探讨了利用RNA和DNA病毒与其宿主共同进化所形成的特性来解决我们这个时代的疾病和其他可持续性问题的生物技术解决方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8239/6613463/aa3db69008f6/CTI2-8-e1067-g001.jpg

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