Inhibition of HIV-1 latency reactivation by dehydroepiandrosterone (DHEA) and an analog of DHEA.
Inhibition of HIV-1 latency reactivation by dehydroepiandrosterone (DHEA) and an analog of DHEA.
复制标题
脱氢表雄酮 (DHEA) 和 DHEA 类似物抑制 HIV-1 潜伏期再激活。
DOI：
10.1089/aid.1993.9.747
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发表时间：
1993
影响因子：
1.5
通讯作者：
Henderson,EE
中科院分区：
文献类型：
--
作者：
Yang,JY;Schwartz,A;Henderson,EE
在大多数个体中，人类免疫缺陷病毒1型（HIV-1）的初始感染通常导致在最终进展为获得性免疫缺陷综合征之前建立潜伏或慢性感染。HIV-1还可以在一些显示最小组成型病毒表达的T细胞系中建立潜伏或持续感染。然而，抗原、有丝分裂原和细胞因子（肿瘤坏死因子α [TNF-α]、白细胞介素1和白细胞介素2）可诱导T细胞系活化，导致HIV-1复制增强。来自其他病毒（HTLV-1、HSV、EBV、CMV、HBV和HHV-6）的各种基因产物也可以增强HIV-1长末端重复序列（LTR）驱动的报告基因活性。基于这些观察，有人提出，潜伏的HIV-1窝藏在慢性感染的T淋巴细胞，单核细胞，或巨噬细胞的再活化在艾滋病的发病机制中起着重要的作用。到目前为止，还没有药物或治疗方法可以提供对HIV-1潜伏期再激活的保护。ACH-2来源于人T细胞系（CEM），被HIV-1慢性感染，具有低水平的组成型病毒表达。ACH-2可通过用12-O-十四烷酰佛醇-13-乙酸酯（TPA）、有丝分裂原或细胞因子（TNF-α）刺激细胞或用HSV感染转化为生产性感染。因此，ACH-2细胞系是研究药物对HIV-1激活影响的良好候选细胞。以前，我们已经报道，DHEA和合成类似物的DHEA可以在植物血凝素刺激的外周血淋巴细胞培养的HIV-1 IIIB复制的适度抑制剂。在这里，我们报告DHEA和DHEA的合成类似物8354，也可以减少ACH-2细胞系中HIV-1的潜伏期再激活。抑制作用不是由于这些药物的细胞毒性。DHEA或8354处理导致TPA或TNF-α刺激的ACH-2细胞系中HIV-1潜伏期再激活下调，通过合胞体形成和逆转录酶活性积累进行测量。抑制机制尚不清楚，但有证据表明NF-κB活化的减少起作用。
The initial infection with human immunodeficiency virus type 1 (HIV-1) in most individuals usually results in the establishment of a latent or chronic infection before eventual progression toward acquired immunodeficiency syndrome. HIV-1 can also establish a latent or persistent infection in some T cell lines that show minimal constitutive virus expression. However, activation of the T cell lines leading to enhanced HIV-1 replication can be induced by antigens, mitogens, and cytokines (tumor necrosis factor α [TNF-α], interleukin 1, and interleukin-2). Various gene products from other viruses (HTLV-1, HSV, EBV, CMV, HBV, and HHV-6) can also enhance HIV-1 long terminal repeat (LTR)-driven reporter gene activity. On the basis of these observations, it has been proposed that reactivation of latent HIV-1 harbored in chronically infected T lymphocytes, monocytes, or macrophages plays an important role in the pathogenesis of AIDS. So far, there are no drugs or therapy available that can provide protection against HIV-1 latency reactivation. ACH-2, derived from a human T cell line (CEM), is chronically infected with HIV-1, with low levels of constitutive virus expression. ACH-2 can be converted to productive infection by stimulation of the cells with 12-O-tetradecanoylphorhol-13-acetate (TPA), mitogen or cytokines (TNF-α), or infection with HSV. Therefore the ACH-2 cell line is a good candidate for studying the effects of drugs on HIV-1 activation. Previously, we have reported that DHEA and synthetic analogs of DHEA can be modest inhibitors of HIV-1 IIIB replication in phytohemagglutinin-stimulated peripheral blood lymphocyte cultures. Here we report that DHEA and a synthetic analog of DHEA, 8354, can also reduce HIV-1 latency reactivation in the ACH-2 cell line. The inhibitory effect is not due to cytotoxicity of these drugs. Treatment with DHEA or 8354 resulted in downregulation of HIV-1 latency reactivation in a TPA- or TNF-α-stimulated ACH-2 cell line as measured by syncytium formation and accumulation of reverse transcriptase activity. The mechanisms of inhibition are not clear, but evidence suggests that reduction of NF-κB activation plays a role.