Darlix J L, Lapadat-Tapolsky M, de Rocquigny H, Roques B P
LaboRetro, Unité de Virologie humaine INSERM U412, Ecole Normale Supérieure de Lyon, France.
J Mol Biol. 1995 Dec 8;254(4):523-37. doi: 10.1006/jmbi.1995.0635.
Retroviruses are a family of widespread small animal viruses about 110 nm in diameter, composed of an inner core surrounded by an outer envelope formed of a lipid bilayer of cellular origin in which are anchored viral glycoproteins. The inner core is formed by an outer shell of capsid protein molecules (CA protein) surrounding the dimeric RNA genome in close association with about 2000 molecules of nucleocapsid protein (NC protein) and molecules of reverse transcriptase (RT) and integrase (IN). Conversion of the genomic single-stranded RNA into a double-stranded proviral DNA by RT takes place in the nucleocapsid substructure and involves two DNA strand transfers to generate the long terminal repeats (LTR) required for IN-mediated integration of the proviral DNA into the cellular genome and its expression. In this review we have summarized some of the properties and functions of the nucleocapsid protein of the most intensely studied oncoretroviruses (MuLV and ASLV) and lentiviruses (HIV-1). Recent biochemical and genetic data on retroviral NC proteins have shown that this small viral protein endowed with a strong affinity for nucleic acids exhibits nucleic acid annealing and strand transfer activities and is required for the formation of infectious viral particles. These new activities of NC protein are most probably necessary at the early steps of proviral DNA synthesis. The 3-D structures of HIV-1 and MoMuLV NC proteins, deduced from NMR studies, are characterized by a central globular domain with one (MoMuLV) or two (HIV-1) zinc fingers. This should facilitate a rational approach of new anti-HIV therapies based on inhibition of NC protein functions. Due to space limitations and the very abundant literature on retroviruses, references to articles prior to the publication of the second volume of RNA Tumor Viruses in 1985 (Weiss et al., 1985) will be minimal. We also direct the reader to an excellent review which summarizes recent insights into biochemical and structural aspects of the retroviral enzymes PR, RT and IN (Katz & Skalka, 1994).
逆转录病毒是一类广泛存在的小型动物病毒，直径约110纳米，由一个内核和一个外膜组成，外膜由细胞来源的脂质双层构成，病毒糖蛋白锚定其中。内核由衣壳蛋白分子（CA蛋白）的外壳围绕二聚体RNA基因组形成，与约2000个核衣壳蛋白（NC蛋白）分子以及逆转录酶（RT）和整合酶（IN）分子紧密结合。RT将基因组单链RNA转化为双链前病毒DNA的过程发生在核衣壳亚结构中，涉及两次DNA链转移以产生IN介导前病毒DNA整合到细胞基因组及其表达所需的长末端重复序列（LTR）。在本综述中，我们总结了研究最为深入的嗜脏器逆转录病毒（鼠白血病病毒和禽肉瘤白血病病毒）和慢病毒（HIV-1）的核衣壳蛋白的一些特性和功能。关于逆转录病毒NC蛋白的最新生化和遗传学数据表明，这种对核酸具有强亲和力的小病毒蛋白具有核酸退火和链转移活性，是感染性病毒颗粒形成所必需的。NC蛋白的这些新活性很可能在病毒DNA合成的早期步骤中是必需的。通过核磁共振研究推导得出的HIV-1和莫洛尼鼠白血病病毒NC蛋白的三维结构，其特征是具有一个（莫洛尼鼠白血病病毒）或两个（HIV-1）锌指的中央球状结构域。这应该有助于基于抑制NC蛋白功能开发新的抗HIV疗法。由于篇幅限制以及关于逆转录病毒的文献非常丰富，对1985年《RNA肿瘤病毒》第二卷出版之前（Weiss等人，1985年）的文章引用将减至最少。我们还引导读者阅读一篇精彩的综述，该综述总结了对逆转录病毒酶PR、RT和IN的生化和结构方面的最新见解（Katz和Skalka，1994年）。
