Onafuwa-Nuga Adewunmi, Telesnitsky Alice
Department of Microbiology and Immunology, University of Michigan Medical School, 1150 West Medical Center Drive, Room 5641, Ann Arbor, MI 48109-5620, USA.
Microbiol Mol Biol Rev. 2009 Sep;73(3):451-80, Table of Contents. doi: 10.1128/MMBR.00012-09.
The genetic diversity of human immunodeficiency virus type 1 (HIV-1) results from a combination of point mutations and genetic recombination, and rates of both processes are unusually high. This review focuses on the mechanisms and outcomes of HIV-1 genetic recombination and on the parameters that make recombination so remarkably frequent. Experimental work has demonstrated that the process that leads to recombination--a copy choice mechanism involving the migration of reverse transcriptase between viral RNA templates--occurs several times on average during every round of HIV-1 DNA synthesis. Key biological factors that lead to high recombination rates for all retroviruses are the recombination-prone nature of their reverse transcription machinery and their pseudodiploid RNA genomes. However, HIV-1 genes recombine even more frequently than do those of many other retroviruses. This reflects the way in which HIV-1 selects genomic RNAs for coencapsidation as well as cell-to-cell transmission properties that lead to unusually frequent associations between distinct viral genotypes. HIV-1 faces strong and changeable selective conditions during replication within patients. The mode of HIV-1 persistence as integrated proviruses and strong selection for defective proviruses in vivo provide conditions for archiving alleles, which can be resuscitated years after initial provirus establishment. Recombination can facilitate drug resistance and may allow superinfecting HIV-1 strains to evade preexisting immune responses, thus adding to challenges in vaccine development. These properties converge to provide HIV-1 with the means, motive, and opportunity to recombine its genetic material at an unprecedented high rate and to allow genetic recombination to serve as one of the highest barriers to HIV-1 eradication.
1型人类免疫缺陷病毒（HIV-1）的基因多样性源于点突变和基因重组的共同作用，且这两个过程的发生率都异常高。本综述聚焦于HIV-1基因重组的机制和结果，以及导致重组异常频繁的参数。实验工作表明，导致重组的过程——一种涉及逆转录酶在病毒RNA模板之间迁移的拷贝选择机制——在HIV-1 DNA合成的每一轮中平均会发生数次。导致所有逆转录病毒重组率高的关键生物学因素是其逆转录机制易于重组的特性及其假二倍体RNA基因组。然而，HIV-1基因的重组甚至比许多其他逆转录病毒的基因更频繁。这反映了HIV-1选择基因组RNA进行共包装的方式以及细胞间传播特性，这些特性导致不同病毒基因型之间异常频繁的关联。HIV-1在患者体内复制期间面临强大且多变的选择条件。HIV-1作为整合前病毒的持续存在模式以及体内对缺陷前病毒的强烈选择为等位基因存档提供了条件，这些等位基因在初始前病毒建立数年之后仍可复苏。重组可促进耐药性，并可能使超感染的HIV-1毒株逃避预先存在的免疫反应，从而增加了疫苗开发的挑战。这些特性共同为HIV-1提供了手段、动机和机会，使其以前所未有的高频率重组其遗传物质，并使基因重组成为HIV-1根除的最大障碍之一。
