Dron M, Hameau L, Benboudjema L, Guymarho J, Cajean-Feroldi C, Rizza P, Godard C, Jasmin C, Tovey M G, Lang M C
Laboratory of Viral Oncology, C.N.R.S., Villejuif, France.
Arch Virol. 1999;144(1):19-28. doi: 10.1007/s007050050482.
To identify the pathways involved in HIV-1 modification of cellular gene expression, chronically infected U937 cells were screened by mRNA differential display. A chimeric transcript consisting of the 3' end of the LTR of a HIV-1 provirus, followed by 3.7 kb of cellular RNA was identified suggesting that long readthrough transcription might be one of the mechanisms by which gene expression could be modified in individual infected cells. Such a phenomenon may also be the first step towards the potential transduction of cellular sequences. Furthermore, the mRNA encoding for the transcription factor Egr-1 was detected as an over-represented transcript in infected cells. Northern blot analysis confirmed the increase of Egr-1 mRNA content in both HIV-1 infected promonocytic U937 cells and T cell lines such as Jurkat and CEM. Interestingly a similar increase of Egr-1 mRNA has previously been reported to occur in HTLV-1 and HTLV-2 infected T cell lines. Despite the consistent increase in the level of Egr-1 mRNA, the amount of the encoded protein did not appear to be modified in HIV-1 infected cells, suggesting an increased turn over of the protein in chronically infected cells.
为了确定参与HIV-1对细胞基因表达进行修饰的途径，通过mRNA差异显示技术对慢性感染的U937细胞进行了筛选。鉴定出一种嵌合转录本，其由HIV-1前病毒LTR的3'末端组成，后面跟着3.7 kb的细胞RNA，这表明长通读转录可能是在单个感染细胞中修饰基因表达的机制之一。这种现象也可能是细胞序列潜在转导的第一步。此外，编码转录因子Egr-1的mRNA在感染细胞中被检测为过度表达的转录本。Northern印迹分析证实，在HIV-1感染的单核细胞U937细胞以及T细胞系（如Jurkat和CEM）中，Egr-1 mRNA含量均增加。有趣的是，先前曾报道在HTLV-1和HTLV-2感染的T细胞系中也出现过类似的Egr-1 mRNA增加情况。尽管Egr-1 mRNA水平持续升高，但在HIV-1感染的细胞中，编码蛋白的量似乎并未发生改变，这表明在慢性感染细胞中该蛋白的周转加快。
