Popik W, Pitha P M
Oncology Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231.
J Virol. 1993 Feb;67(2):1094-9. doi: 10.1128/JVI.67.2.1094-1099.1993.
Transcription of human immunodeficiency virus type 1 (HIV-1) depends on the function of the virus-encoded regulatory protein Tat, which interacts with the specific Tat response (TAR) element present in the leader sequence of all HIV-1 RNAs. In this study, we examined whether tumor necrosis factor alpha (TNF-alpha) can replace the requirement for a functional Tat protein. We found that TNF-alpha can induce expression of a latent, tat-defective virus and support its replication both in T cells and in primary mononuclear cells. Analysis of the transcriptional rate of the tat-defective HIV-1 transcriptional unit indicates that TNF-alpha stimulates the initiation of transcription but, in contrast to Tat protein, does not significantly reduce transcriptional polarity. Interestingly, we found that the processing of viral precursor proteins is altered in the absence of Tat. We propose that TNF-alpha-mediated induction of HIV-1 plays an essential role in the early stages of the virus life cycle and in viral latency.
1型人类免疫缺陷病毒（HIV-1）的转录依赖于病毒编码的调节蛋白Tat的功能，该蛋白与所有HIV-1 RNA前导序列中存在的特定Tat反应（TAR）元件相互作用。在本研究中，我们检测了肿瘤坏死因子α（TNF-α）是否可以替代对功能性Tat蛋白的需求。我们发现TNF-α可以诱导潜伏的、tat缺陷型病毒的表达，并在T细胞和原代单核细胞中支持其复制。对tat缺陷型HIV-1转录单元转录速率的分析表明，TNF-α刺激转录起始，但与Tat蛋白不同的是，它不会显著降低转录极性。有趣的是，我们发现在没有Tat的情况下，病毒前体蛋白的加工会发生改变。我们提出，TNF-α介导的HIV-1诱导在病毒生命周期的早期阶段和病毒潜伏中起着至关重要的作用。
