INHIBITION OF HIV ACTIVATION BY SOLUBLE TUMOR NECROSIS FACTOR RECEPTOR

炎症细胞因子，肿瘤坏死因子-α（TNF-α）， 在慢性和急性感染中刺激HIV-1复制 感染的T淋巴细胞和单核细胞。 艾滋病毒长的激活 末端重复序列（HIV-LTR）和随后的病毒产量增加， 与TNF激活细胞转录因子NF-κ B有关。 我们 已经测试了两种形式的可溶性重组1型（p80） TNF受体抑制TNF诱导的HIV体外活化。 的一种形式 受体是含有完整的234个残基的单体， p80的胞外（配体结合）部分。 第二种形式是 同源二聚体嵌合蛋白，其含有这些相同的残基， 截短的人IgG（I）免疫球蛋白链，因此类似于 无轻链的二价抗体。 这些重组蛋白是 测试它们抑制TNF-α诱导的HIV-1表达的能力 在慢性感染的人细胞系中，如通过病毒逆转录所确定的， 转录酶活性 我们还检查了可溶性 受体来限制HIV-LTR转录的激活。 可溶性 TNF受体二聚体在阻断TNF-α诱导的细胞凋亡方面最有效。 在单核细胞和淋巴细胞细胞系中表达。 的比率 TNF-α受体至关重要，最佳抑制需要 10-倍过量的受体。 单体受体的作用较低， 阻断，有时，能够增强 TNF-α 因此，我们的数据表明，TNF-α诱导的HIV-1 可以使用TNF的二聚体形式在体外限制表达 受体在特定比例超过TNF-α。

The inflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), has been shown to stimulate HIV-1 replication in both chronically and acutely infected T-lymphocytes and monocytes. The activation of the HIV-Long Terminal Repeat (HIV-LTR) and subsequent increase in virus production is linked to TNF activation of the cellular transcription factor, NF-kB. We have tested the ability of two forms of soluble recombinant type 1 (p80) TNF receptor to inhibit TNF-induced HIV activation in vitro. One form of the receptor is a monomer containing the entire 234 residues of the extracellular (ligand-binding) portion of p80. A second form is a homodimer chimeric protein containing these same residues fused to a truncated human IgG(l) immunoglobulin chain, and thus resembles a bivalent antibody without light chains. These recombinant proteins were tested for their ability to inhibit TNF-alpha-induced expression of HIV-1 in chronically infected human cell lines as determined by viral reverse transcriptase activity. We also examined the ability of the soluble receptors to limit the activation of HIV-LTR transcription. The soluble TNF receptor dimer was most effective at blocking the TNF-alpha-induced expression in both monocytic and lymphocytic cell lines. The ratio of receptor to TNF-alpha was critical, with optimal inhibition requiring a 10-fold excess of receptor. Monomeric receptor was less effective at blocking and, at times, was capable of augmenting the activity of TNF-alpha. Thus, our data suggests that TNF-alpha-induced HIV-1 expression can be limited in vitro using a dimeric form of the TNF receptor at specific ratios in excess of TNF-alpha.