Winslow B J, Pomerantz R J, Bagasra O, Trono D
Infectious Disease Laboratory, Salk Institute, La Jolla, California 92037-1099.
Virology. 1993 Oct;196(2):849-54. doi: 10.1006/viro.1993.1545.
Cell lines that are nonproductively infected with human immunodeficiency virus type 1 (HIV-1), such as the T-lymphocyte ACH2 clone, have been proposed to represent in vitro models of proviral latency. We have previously shown that such cells exhibit an aberrant pattern of viral RNA expression, with a large excess of fully spliced viral RNAs. Here, by superinfecting the ACH2 cells with a second HIV-1 virus, we demonstrate the primary mechanism of HIV-1 proviral latency in this cell line. In the dually infected cells, the exogenous virus was transcribed at high levels. However, expression from the provirus originally present in the ACH2 cells was not quantitatively increased. Still, its RNA production was shifted from a blocked early-stage to a fully productive pattern. This was interpreted to be a consequence of the high levels of Rev produced by the exogenous virus, acting in trans to promote the cytoplasmic export of all incompletely spliced viral mRNAs made in the cells. Comparable numbers of copies of each provirus were present in the dually infected cells, and both viruses grew equally well, once passed onto fresh cells. These results indicate that the low levels of transcriptional activity of the HIV-1 virus present in ACH2 cells are secondary to specific characteristics of the region of the cellular genome in which the proviral DNA is integrated.
已有人提出，诸如T淋巴细胞ACH2克隆之类的被1型人类免疫缺陷病毒（HIV-1）非生产性感染的细胞系可代表原病毒潜伏的体外模型。我们先前已表明，此类细胞呈现出异常的病毒RNA表达模式，其中完全剪接的病毒RNA大量过剩。在此，通过用第二种HIV-1病毒对ACH2细胞进行超感染，我们证明了该细胞系中HIV-1原病毒潜伏的主要机制。在双重感染的细胞中，外源病毒高水平转录。然而，原本存在于ACH2细胞中的原病毒的表达并未在数量上增加。不过，其RNA产生从受阻的早期阶段转变为完全有效的模式。这被解释为外源病毒产生的高水平Rev的结果，Rev通过反式作用促进细胞中产生的所有不完全剪接的病毒mRNA的细胞质输出。双重感染的细胞中每种原病毒的拷贝数相当，并且一旦传代到新鲜细胞上，两种病毒生长得同样良好。这些结果表明，ACH2细胞中存在的HIV-1病毒转录活性低是原病毒DNA整合所在的细胞基因组区域的特定特征所致。
