Cloning of a long HIV-1 readthrough transcript and detection of an increased level of early growth response protein-1 (Egr-1) mRNA in chronically infected U937 cells

To identify the pathways involved in HIV-1 modification of cellular gene ex pression, chronically infected U937 cells were screened by mRNA differentia l display. A chimeric transcript consisting of the 3' end of the LTR of a H IV-1 provirus, followed by 3.7 kb of cellular RNA was identified suggesting that long readthrough transcription might be one of the mechanisms by whic h gene expression could be modified in individual infected cells. Such a ph enomenon may also be the first step towards the potential transduction of c ellular sequences. Furthermore, the mRNA encoding for the transcription fac tor Egr-1 was detected as an over-represented transcript in infected cells. Northern blot analysis confirmed the increase of Egr-1 mRNA content in bot h HIV-1 infected promonocytic U937 cells and T cell lines such as Jurkat an d GEM. Interestingly a similar increase of Egr-1 mRNA has previously been r eported to occur in HTLV-1 and HTLV-2 infected T cell lines. Despite the co nsistant increase in the level of Egr-1 mRNA, the amount of the encoded pro tein did not appear to be modified in HIV-1 infected cells, suggesting an i ncreased turn over of the protein in chronically infected cells.