Inoue M, Hoxie J A, Reddy M V, Srinivasan A, Reddy E P
Wistar Institute, Philadelphia, PA.
Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2278-82. doi: 10.1073/pnas.88.6.2278.
The human immunodeficiency virus (HIV) is the etiological agent of acquired immunodeficiency syndrome (AIDS). HIV exhibits extensive genetic diversity and it is apparent that an infected individual contains different populations of distinct viral strains, a large proportion of which has been found surprisingly to be defective for replication. A similar phenomenon has also been observed with some cell lines that are known to produce infectious viral particles but harbor defective proviral genomes. Here, we investigated the molecular basis of this phenomenon by cloning proviral genomes of HIV from a cell line that was capable of producing high titers of biologically active HIV particles that readily induced syncytia with CD4+ cell lines and peripheral blood lymphocytes. This cell line was found to contain five proviral genomes, all of which, when tested individually, failed to produce replication-competent viruses upon transfection into human cells. However, when a specific combination of two proviral genomes was used in such transfection studies, it was possible to obtain biologically active, replication-competent viral particles that infected and replicated in CD4+ cell lines and induced syncytia characteristic of HIV. Such a result may be due to homologous recombination between proviral DNAs occurring in cells after transfection and/or complementation of replication-defective proviral DNAs. The diploid nature of the viral RNA genome present in the viral particle may enable the persistence of defective HIV genomes.
人类免疫缺陷病毒（HIV）是获得性免疫缺陷综合征（AIDS）的病原体。HIV表现出广泛的遗传多样性，很明显，受感染个体含有不同的病毒株群体，其中很大一部分被惊人地发现复制存在缺陷。在一些已知能产生传染性病毒颗粒但含有缺陷前病毒基因组的细胞系中也观察到了类似现象。在此，我们通过从一个能够产生高滴度具有生物活性的HIV颗粒（这些颗粒能轻易与CD4 +细胞系和外周血淋巴细胞诱导形成多核巨细胞）的细胞系中克隆HIV前病毒基因组，来研究这一现象的分子基础。发现该细胞系含有五个前病毒基因组，在转染到人类细胞中时，单独测试时所有这些基因组都无法产生具有复制能力的病毒。然而，当在这种转染研究中使用两个前病毒基因组的特定组合时，就有可能获得具有生物活性、具有复制能力的病毒颗粒，这些颗粒能在CD4 +细胞系中感染和复制，并诱导出HIV特有的多核巨细胞。这样的结果可能是由于转染后细胞中前病毒DNA之间发生同源重组和/或复制缺陷的前病毒DNA互补所致。病毒颗粒中存在的病毒RNA基因组的二倍体性质可能使缺陷HIV基因组得以持续存在。
