MECHANISMS ASSOCIATED WITH THE GENERATION OF BIOLOGICALLY-ACTIVE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 PARTICLES FROM DEFECTIVE PROVIRUSES
MECHANISMS ASSOCIATED WITH THE GENERATION OF BIOLOGICALLY-ACTIVE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 PARTICLES FROM DEFECTIVE PROVIRUSES
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DOI：
10.1073/pnas.88.6.2278
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发表时间：
1991-03-01
影响因子：
11.1
通讯作者：
REDDY, EP
中科院分区：
文献类型：
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作者：
INOUE, M;HOXIE, JA;REDDY, EP
人类免疫缺陷病毒（HIV）是获得性免疫缺陷综合症（AIDS）的病原体。 HIV表现出广泛的遗传多样性，很明显，受感染的个体含有不同病毒株的不同群体，令人惊讶的是，其中很大一部分被发现存在复制缺陷。 在一些已知能产生传染性病毒颗粒但含有有缺陷的原病毒基因组的细胞系中也观察到了类似的现象。 在这里，我们通过从能够产生高滴度的生物活性HIV颗粒的细胞系中克隆HIV前病毒基因组来研究这种现象的分子基础，这些颗粒很容易诱导与CD4+细胞系和外周血淋巴细胞的合胞体。 人们发现该细胞含有五个原病毒基因组，所有这些基因组在单独测试时，在转染到人体细胞后都无法产生具有复制能力的病毒。 然而，当在此类转染研究中使用两种原病毒基因组的特定组合时，可以获得具有生物活性、具有复制能力的病毒颗粒，该病毒颗粒可在CD4+细胞系中感染和复制，并诱导HIV特征的合胞体。 这样的结果可能是由于转染后tr细胞后的细胞中发生的原病毒DNA之间发生的同源重组和/或复制缺陷型原病毒DNA的互补。 病毒颗粒中存在的病毒RNA基因组的二倍体性质可能使有缺陷的HIV基因组得以持续存在。
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 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 tr 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.