Inhibition of HIV activation in latently infected cells by flavonoid compounds
Inhibition of HIV activation in latently infected cells by flavonoid compounds
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DOI：
10.1089/aid.1996.12.39
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发表时间：
1996-01-01
影响因子：
1.5
通讯作者：
Folks, TM
中科院分区：
文献类型：
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作者：
Critchfield, JW;Butera, ST;Folks, TM
H9和C8166培养物的急性HIV-1感染已被某些黄酮类化合物抑制，并且黄酮类化合物还存在抑制HIV-1蛋白酶、整合酶和逆转录酶的证据。本研究的目的是确定黄酮类化合物是否在潜伏感染模型中抑制HIV-1的激活。这三种化合物的生长抑制作用（治疗指数5-10）对HIV活化具有良好的抑制作用，Chrysin在OM-10.1细胞、tnf - α或PMA刺激的ACH-2细胞和8E5培养物中对PMA的反应也能抑制HIV表达。在先前暴露于TNF- α的OM-10.1细胞中，当加入chrysin时，病毒潜伏期会在更短的时间间隔内恢复。HIV活化的抑制不依赖于与黄酮相对于TNF的预孵生，并且以缺乏HIV RNA积累为特征。Northern分析显示，凝胶转移实验显示TNF- α处理后nf - κ B的活化不受这些药物的抑制。这些发现表明，黄酮类化合物通过一种新机制抑制HIV-1的激活，这些药物是旨在维持HIV-1细胞潜伏状态的治疗策略的潜在候选药物。
Acute HIV-1 infection of H9 and C8166 cultures has been shown to be suppressed by certain flavonoids, and evidence for inhibition of HIV-1 protease, integrase, and reverse transcriptase by flavonoids also exists, The present aim was to determine whether flavonoids inhibit HIV-1 activation in models of latent infection, By screening flavonoids from six different classes, three structurally related compounds (chrysin, acacetin, and apigenin) were identified that inhibited HIV expression in TNF-alpha-treated OM-10.1 cultures, The three compounds had favorable potencies against HIV activation in relation to their growth inhibitory effects (therapeutic index 5-10), Chrysin also inhibited HIV expression in response to PMA in OM-10.1 cells, in ACH-2 cells stimulated with either TNF-alpha or PMA, and in 8E5 cultures, Furthermore, return to viral latency in OM-10.1 cells previously exposed to TNF-alpha occurred over a shorter time interval when chrysin was added, The inhibition of HIV activation was not dependent on preincubation with flavonoids relative to TNF, and was characterized by a lack of HIV RNA accumulation by Northern analysis, Gel-shift experiments revealed that NF-kappa B activation after TNF-alpha treatment was not inhibited by these agents, suggesting that some other critical factor(s) needed for viral transcription was being affected, These findings indicate that flavonoids inhibit HIV-1 activation via a novel mechanism, and that these agents are potential candidates for therapeutic strategies aimed at maintaining a cellular state of HIV-1 latency.