hiv - 1复制。

E O Freed
{"title":"hiv - 1复制。","authors":"E O Freed","doi":"10.1023/a:1021070512287","DOIUrl":null,"url":null,"abstract":"<p><p>In general terms, the replication cycle of lentiviruses, including HIV-1, closely resembles that of other retroviruses. There are, however, a number of unique aspects of HIV replication; for example, the HIVs and SIVs target receptors and coreceptors distinct from those used by other retroviruses. Lentiviruses encode a number of regulatory and accessory proteins not encoded by the genomes of the prototypical \"simple\" retroviruses. Of particular interest from the gene therapy perspective, lentiviruses possess the ability to productively infect some types of non-dividing cells. This chapter, while reiterating certain points discussed in Chapter 1, will attempt to focus on issues unique to HIV-1 replication. The HIV-1 genome encodes the major structural and non-structural proteins common to all replication-competent retroviruses (Fig. 1, and Chapter 1). From the 5'- to 3'-ends of the genome are found the gag (for group-specific antigen), pol (for polymerase), and env (for envelope glycoprotein) genes. The gag gene encodes a polyprotein precursor whose name, Pr55Gag, is based on its molecular weight. Pr55Gag is cleaved by the viral protease (PR) to the mature Gag proteins matrix (also known as MA or p17), capsid (CA or p24), nucleocapsid (NC or p7), and p6. Two spacer peptides, p2 and p1, are also generated upon Pr55Gag processing. The pol-encoded enzymes are initially synthesized as part of a large polyprotein precursor, Pr160GagPol, whose synthesis results from a rare frameshifting event during Pr55Gag translation. The individual pol-encoded enzymes, PR, reverse transcriptase (RT), and integrase (IN), are cleaved from Pr160GagPol by the viral PR. The envelope (Env) glycoproteins are also synthesized as a polyprotein precursor (Fig. 1). Unlike the Gag and Pol precursors, which are cleaved by the viral PR, the Env precursor, known as gp160, is processed by a cellular protease during Env trafficking to the cell surface, gp160 processing results in the generation of the surface (SU) Env glycoprotein gp120 and the transmembrane (TM) glycoprotein gp41. gp120 contains the determinants that interact with receptor and coreceptor, while gp41 not only anchors the gp120/gp41 complex in the membrane (Fig. 2), but also contains domains that are critical for catalyzing the membrane fusion reaction between viral and host lipid bilayers during virus entry. Comparison of env sequences from a large number of virus isolates revealed that gp120 is organized into five conserved regions (C1-C5) and five highly variable domains (V1-V5). 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引用次数: 368

摘要

一般来说,包括HIV-1在内的慢病毒的复制周期与其他逆转录病毒非常相似。然而,艾滋病毒复制有许多独特的方面;例如,hiv和siv靶向的受体和辅受体与其他逆转录病毒使用的受体和辅受体不同。慢病毒编码一些“简单”逆转录病毒原型基因组不编码的调节蛋白和辅助蛋白。从基因治疗的角度来看,慢病毒具有有效感染某些类型的非分裂细胞的能力。本章在重申第1章中讨论的某些要点的同时,将试图集中讨论HIV-1复制所特有的问题。HIV-1基因组编码所有具有复制能力的逆转录病毒共有的主要结构蛋白和非结构蛋白(图1和第1章)。在基因组的5′- 3′端,发现了gag(群体特异性抗原)、pol(聚合酶)和env(包膜糖蛋白)基因。gag基因编码一种多蛋白前体,其名称Pr55Gag是基于其分子量。Pr55Gag被病毒蛋白酶(PR)切割成成熟的Gag蛋白基质(也称为MA或p17)、衣壳(CA或p24)、核衣壳(NC或p7)和p6。两个间隔肽p2和p1也在Pr55Gag处理过程中产生。pol编码酶最初是作为一个大的多蛋白前体Pr160GagPol的一部分合成的,其合成源于Pr55Gag翻译过程中罕见的帧移事件。单独的Pol编码酶PR、逆转录酶(RT)和整合酶(IN)被病毒PR从Pr160GagPol中切割出来。包膜(Env)糖蛋白也被合成为多蛋白前体(图1)。与Gag和Pol前体(由病毒PR切割)不同,Env前体(称为gp160)在Env运输到细胞表面期间由细胞蛋白酶处理。gp160的处理导致表面(SU) Env糖蛋白gp120和跨膜(TM)糖蛋白gp41的产生。gp120包含与受体和辅受体相互作用的决定因子,而gp41不仅在膜上锚定gp120/gp41复合物(图2),而且还包含在病毒进入时催化病毒和宿主脂质双层之间的膜融合反应的关键结构域。与大量病毒分离株的env序列比较发现,gp120被组织成5个保守区域(C1-C5)和5个高度可变结构域(V1-V5)。可变区域往往位于二硫化物连接的环中。Gp41由三个主要结构域组成:外结构域(包含膜融合所必需的决定因子)、跨膜锚定序列和细胞质尾部。除了gag、pol和env基因外,HIV-1还编码许多调节蛋白和辅助蛋白。这对HIV-1 LTR的转录至关重要,而Rev在病毒rna从细胞核转运到细胞质的过程中起着重要作用。Vpu、Vif、Vpr和Nef被称为“辅助”或“辅助”蛋白,以反映病毒复制并不统一需要它们这一事实。这些非常有趣的蛋白质的功能将在本章的末尾进行更详细的讨论。HIV的复制过程可以分为两个阶段:“早期”和“晚期”(图3)。尽管一些事件以协调一致或同时发生的方式发生,但复制周期可以最简单地视为有序的、循序渐进的方式进行。在本章中,将考虑病毒复制的每个步骤;其他信息可以从更详细的评论和引用的主要参考文献中获得。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
HIV-1 replication.

In general terms, the replication cycle of lentiviruses, including HIV-1, closely resembles that of other retroviruses. There are, however, a number of unique aspects of HIV replication; for example, the HIVs and SIVs target receptors and coreceptors distinct from those used by other retroviruses. Lentiviruses encode a number of regulatory and accessory proteins not encoded by the genomes of the prototypical "simple" retroviruses. Of particular interest from the gene therapy perspective, lentiviruses possess the ability to productively infect some types of non-dividing cells. This chapter, while reiterating certain points discussed in Chapter 1, will attempt to focus on issues unique to HIV-1 replication. The HIV-1 genome encodes the major structural and non-structural proteins common to all replication-competent retroviruses (Fig. 1, and Chapter 1). From the 5'- to 3'-ends of the genome are found the gag (for group-specific antigen), pol (for polymerase), and env (for envelope glycoprotein) genes. The gag gene encodes a polyprotein precursor whose name, Pr55Gag, is based on its molecular weight. Pr55Gag is cleaved by the viral protease (PR) to the mature Gag proteins matrix (also known as MA or p17), capsid (CA or p24), nucleocapsid (NC or p7), and p6. Two spacer peptides, p2 and p1, are also generated upon Pr55Gag processing. The pol-encoded enzymes are initially synthesized as part of a large polyprotein precursor, Pr160GagPol, whose synthesis results from a rare frameshifting event during Pr55Gag translation. The individual pol-encoded enzymes, PR, reverse transcriptase (RT), and integrase (IN), are cleaved from Pr160GagPol by the viral PR. The envelope (Env) glycoproteins are also synthesized as a polyprotein precursor (Fig. 1). Unlike the Gag and Pol precursors, which are cleaved by the viral PR, the Env precursor, known as gp160, is processed by a cellular protease during Env trafficking to the cell surface, gp160 processing results in the generation of the surface (SU) Env glycoprotein gp120 and the transmembrane (TM) glycoprotein gp41. gp120 contains the determinants that interact with receptor and coreceptor, while gp41 not only anchors the gp120/gp41 complex in the membrane (Fig. 2), but also contains domains that are critical for catalyzing the membrane fusion reaction between viral and host lipid bilayers during virus entry. Comparison of env sequences from a large number of virus isolates revealed that gp120 is organized into five conserved regions (C1-C5) and five highly variable domains (V1-V5). The variable regions tend to be located in disulfide-linked loops. gp41 is composed of three major domains: the ectodomain (which contains determinants essential for membrane fusion), the transmembrane anchor sequence, and the cytoplasmic tail. In addition to the gag, pol, and env genes, HIV-1 also encodes a number of regulatory and accessory proteins. Tat is critical for transcription from the HIV-1 LTR and Rev plays a major [figure: see text] role in the transport of viral RNAs from the nucleus to the cytoplasm. Vpu, Vif, Vpr and Nef have been termed "accessory" or "auxiliary" proteins to reflect the fact that they are not uniformly required for virus replication. The functions of these very interesting proteins will be discussed in more detail at the end of this chapter. HIV replication proceeds in a series of events that can be divided into two overall phases: "early" and "late" (Fig. 3). Although some events occur in a concerted or simultaneous fashion, the replication cycle can be viewed most simply as proceeding in an ordered, step-wise manner. In this chapter, each step in virus replication will be considered; additional information can be obtained from the more detailed reviews and primary references that are cited.

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