INACTIVATION OF THE HUMAN-IMMUNODEFICIENCY-VIRUS BY HYPERICIN - EVIDENCE FOR PHOTOCHEMICAL ALTERATIONS OF P24 AND A BLOCK IN UNCOATING
INACTIVATION OF THE HUMAN-IMMUNODEFICIENCY-VIRUS BY HYPERICIN - EVIDENCE FOR PHOTOCHEMICAL ALTERATIONS OF P24 AND A BLOCK IN UNCOATING
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DOI：
10.1089/aid.1992.8.1929
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发表时间：
1992-11-01
影响因子：
1.5
通讯作者：
MERUELO, D
中科院分区：
文献类型：
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作者：
DEGAR, S;PRINCE, AM;MERUELO, D
人类免疫缺陷病毒 (HIV) 附着并进入宿主细胞后，HIV 基因组 RNA 被逆转录为 cDNA。该步骤可能被金丝桃素抑制，金丝桃素是一种诱导逆转录病毒衣壳改变的化合物。 HIV与金丝桃素一起孵育使病毒失去传染性。 HIV的复制被早期阻止；在用金丝桃素处理的 HIV 攻击的细胞中无法检测到 HIV cDNA。金丝桃素不抑制重组gp120与CD4+细胞的结合，金丝桃素也不抑制合胞体形成。然而，金丝桃素处理的病毒颗粒无法释放逆转录酶活性。蛋白质印迹分析显示，金丝桃素治疗后，HIV 主要衣壳蛋白 (p24) 的活动性发生改变。金丝桃素处理的重组 HIV p24 表现出类似的迁移性改变。 HIV 感染性的灭活和 p24 迁移性的改变需要金丝桃素在可见光下孵育。总的来说，这些数据表明 HIV 衣壳的光化学改变可能有助于金丝桃素介导的 HIV 灭活。这种改变可能会抑制经过治疗的HIV释放RT活性，并防止靶细胞内HIV基因组的脱壳和随后的逆转录。
Following attachment and entry of human immunodeficiency virus (HIV) into a host cell, the HIV genomic RNA is reverse transcribed to cDNA. This step may be inhibited by hypericin, a compound that induces alterations of the retroviral capsid. Incubation of HIV with hypericin rendered the virus noninfectious. The replication of HIV was blocked early; HIV cDNA could not be detected in cells challenged with hypericin-treated HIV. Hypericin did not inhibit the binding of recombinant gp120 to CD4+ cells, nor did hypericin inhibit syncytium formation. However, reverse transcriptase activity could not be released from hypericin-treated virions. Western blot analysis revealed altered mobility of the HIV major capsid protein (p24) following hypericin treatment. Hypericin-treated recombinant HIV p24 exhibited similar altered mobility. The inactivation of HIV infectivity and the alterations in p24 mobility required hypericin incubations in the presence of visible light. Collectively, these data suggest that photochemical alterations of the HIV capsid may contribute to the hypericin-mediated inactivation of HIV. Such alterations may inhibit the release of RT activity from treated HIV, and prevent uncoating and subsequent reverse transcription of the HIV genome within a target cell.