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. 1994 Apr;68(4):2726–2730. doi: 10.1128/jvi.68.4.2726-2730.1994

Human immunodeficiency virus type 1 RNA expression by four chronically infected cell lines indicates multiple mechanisms of latency.

S T Butera 1, B D Roberts 1, L Lam 1, T Hodge 1, T M Folks 1
PMCID: PMC236750  PMID: 7511177

Abstract

Recent information has suggested that posttranscriptional mechanisms, whereby human immunodeficiency virus type 1 (HIV-1) RNA exists as multiply spliced transcripts without promoting an accumulation of the larger messages, are responsible for maintaining a stable state of nonproductive viral expression or viral latency. To test the universality of these observations, we compared the patterns of viral RNA splicing and the frequencies of cells actually harboring HIV-1 RNA in four chronically HIV-1-infected cell lines (U1 [promonocytic], ACH-2 [T lymphocytic], OM-10.1 [promyelocytic], and J1.1 [T lymphocytic]). In uninduced U1 and ACH-2 cultures, a high frequency of cells (approximately one in six) contained HIV-1 RNA but mainly as multiply spliced transcripts, again supporting a posttranscriptional mechanism maintaining viral latency. In sharp contrast, only 1 in 50 cells in uninduced OM-10.1 and J1.1 cultures contained HIV-1 RNA, indicating a primary transcriptional mechanism controlling viral expression in these cells. Furthermore, those OM-10.1 and J1.1 cells that did contain viral RNA were in a state of productive HIV-1 expression marked by the presence of both spliced and unspliced transcripts. Even though the total absence of viral RNA in the majority of OM-10.1 and J1.1 cells indicated a state of absolute latency, treatment with tumor necrosis factor alpha induced transcription of HIV-1 RNA in nearly 100% of the cells in all four of the chronically infected cultures. Tumor necrosis factor alpha induction of U1, ACH-2, and OM-10.1 cultures resulted in an initial accumulation of multiply spliced HIV-1 RNA followed by a transition to the larger unspliced viral RNA transcripts. This RNA splice transition was less apparent in the J1.1 cell line. These results demonstrate that host cell-specific transcriptional and posttranscriptional mechanisms are important factors in the control of HIV-1 latency.

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Selected References

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