Inhibition of HIV-1 in cell culture by synthetic humate analogues derived from hydroquinone: Mechanism of inhibition
Inhibition of HIV-1 in cell culture by synthetic humate analogues derived from hydroquinone: Mechanism of inhibition
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DOI：
10.1006/viro.1996.0208
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发表时间：
1996-04-15
期刊：
影响因子：
3.7
通讯作者：
Riede, UN
中科院分区：
文献类型：
--
作者：
Schneider, J;Weis, R;Riede, UN
腐殖酸是土壤和地下水的天然成分，主要由多环酚类化合物的混合物组成。通过氧化对苯二酚合成了一种平均分子量约为1000 Da的类似化合物复合物，命名为HS-1500。HS-1500抑制MT-2细胞的HIV-1感染，IC 50为50-300 ng/ml，平均细胞毒性约为600 μ g/ml。在10-50 μ g/ml时观察到HIV诱导的合胞体形成的抑制。用HS-1500处理游离的和细胞附着的HIV不可逆地降低了其感染性，而靶细胞对病毒的易感性在感染前并没有受到损害。HIV包膜蛋白gp 120 SU与HS-1500凝胶结合后，可被高盐和去污剂洗脱。HS-1500干扰CD 4诱导的病毒体gp 120 SU的vs环的蛋白水解切割。此外，V3环特异性抗体的结合被不可逆地抑制，而可溶性GD 4与病毒和感染细胞上的gp 120 SU的结合不受影响。总之，我们的数据表明，合成腐殖酸类似物通过干扰V3环介导的病毒进入步骤来抑制HIV颗粒的感染性。(C)出版社：Academic Press，Inc.
Humic acids are natural constituents of soil and ground water and mainly consist of mixtures of polycyclic phenolic compounds. A similar complex of compounds with a mean size of about 1000 Da, designated HS-1500, was synthesized by oxidation of hydroquinone. HS-1500 inhibited HIV-1 infection of MT-2 cells with an IC50 of 50-300 ng/ml and showed a mean cell toxicity of about 600 mu g/ml. Inhibition of HIV-induced syncytium formation was observed at 10-50 mu g/ml. Treatment of free and cell-attached HIV with HS-1500 irreversibly reduced its infectivity, whereas the susceptibility of target cells for the virus was not impaired by treatment prior to infection. The HIV envelope protein gp120SU bound to sepharose-coupled HS-1500 and could be eluted by high salt and detergent. HS-1500 interfered with the CD4-induced proteolytic cleavage of the vs loop of virion gp120SU. Furthermore, binding of V3 loop-specific antibodies was irreversibly inhibited, whereas binding of soluble GD4 to gp120SU on virus and infected cells was not affected. In conclusion, our data suggest, that the synthetic humic acid analogue inhibits the infectivity of HIV particles by interference with a V3 loop-mediated step of virus entry. (C) 1996 Academic Press, Inc.