RNA-Mediated Virus Assembly: Mechanisms and Consequences for Viral Evolution and Therapy.

RNA-Mediated Virus Assembly: Mechanisms and Consequences for Viral Evolution and Therapy.
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DOI:
10.1146/annurev-biophys-052118-115611
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发表时间:
2019-05-06
影响因子:
12.4
通讯作者:
Stockley PG
Stockley PG
中科院分区:
生物学1区
文献类型:
--
作者:
Twarock R;Stockley PG

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病毒,由核酸,蛋白质和在某些情况下脂质组成的实体缺乏在其靶细胞外复制的能力。它们的组成部分在纳米尺度上以极高的精度自我组装这是它们在感染中取得生物学成功的关键。结构测定和生物物理工具的发展,如单分子光谱学和非共价质谱的最新进展允许前所未有的访问简单病毒体的详细组装机制。将这些技术与数学建模和生物信息学相结合,揭示了基因组RNA在调节病毒衣壳形成中的一个先前未被怀疑的作用,揭示了多个分散的RNA序列/结构基序[包装信号(PS)],这些基序协同结合同源外壳蛋白。PS系综控制组装效率,并解释了体内观察到的包装特异性。PS的确切作用模式在不同的病毒家族之间存在差异,但这一共同原则适用于许多病毒家族,包括主要的人类病原体。这些见解开辟了机会,以阻止或重新组装PS功能的新的抗病毒治疗和基因/药物/疫苗的应用。
Viruses, entities composed of nucleic acids, proteins, and in some cases lipids lack the ability to replicate outside their target cells. Their components self-assemble at the nanoscale with exquisite precision—a key to their biological success in infection. Recent advances in structure determination and the development of biophysical tools such as single-molecule spectroscopy and noncovalent mass spectrometry allow unprecedented access to the detailed assembly mechanisms of simple virions. Coupling these techniques with mathematical modeling and bioinformatics has uncovered a previously unsuspected role for genomic RNA in regulating formation of viral capsids, revealing multiple, dispersed RNA sequence/structure motifs [packaging signals (PSs)] that bind cognate coat proteins cooperatively. The PS ensemble controls assembly efficiency and accounts for the packaging specificity seen in vivo. The precise modes of action of the PSs vary between viral families, but this common principle applies across many viral families, including major human pathogens. These insights open up the opportunity to block or repurpose PS function in assembly for both novel antiviral therapy and gene/drug/vaccine applications.
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