Tripeptide interference with human immunodeficiency virus type 1 morphogenesis
Tripeptide interference with human immunodeficiency virus type 1 morphogenesis
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DOI：
10.1128/aac.46.11.3597-3605.2002
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发表时间：
2002-11-01
影响因子：
4.9
通讯作者：
Vahlne, A
中科院分区：
文献类型：
--
作者：
Höglund, S;Su, J;Vahlne, A
病毒复制过程中的衣壳组装是抗病毒治疗的潜在靶点。Gag多蛋白是逆转录病毒颗粒的主要结构成分，在人类免疫缺陷病毒1型（HIV-1）中，它包含基质、衣壳、核衣壳和一些小多肽的序列。在这里，我们报道了在100 p，M的浓度下，HIV-1衣壳蛋白p24羧基末端序列的83个三肽酰胺中的7个抑制了HIV-1的复制（>80%）。三种最有效的三肽，甘氨酸-脯氨酸-甘氨酸酰胺。（GPG-NH2）、丙氨酰-亮氨酸-甘氨酸酰胺（ALG-NH2）和精氨酸酰-谷氨酰-甘氨酸酰胺（RQG-NH2）与p24相互作用。电镜观察发现，当细胞被GPG-NH2和ALG-NH2处理时，HIV-1子代的核心结构被广泛地破坏。此外，仅在处理细胞的质膜上观察到与HIV-1锥形衣壳宽端大致相同大小的结节结构，这可能表明出芽过程被阻止。相应的具有非修饰羧基末端的三肽没有生物活性，也不与p24相互作用。
Capsid assembly during virus replication is a potential target for antiviral therapy. The Gag polyprotein is the main structural component of retroviral particles, and in human immunodeficiency virus type 1 (HIV-1), it contains the sequences for the matrix, capsid, nucleocapsid, and several small polypeptides. Here, we report that at a concentration of 100 p,M, 7 of 83 tripeptide amides from the carboxyl-terminal sequence of the HIV-1 capsid protein p24 suppressed HIV-1 replication (>80%). The three most potent tripeptides, glycyl-prolylglycine-amide. (GPG-NH2), alanyl-leucyl-glycine-amide (ALG-NH2), and arginyl-glutaminyl-glycine-amide (RQG-NH2), were found to interact with p24. With electron microscopy, disarranged core structures of HIV-1 progeny were extensively observed when the cells were treated with GPG-NH2 and ALG-NH2. Furthermore, nodular structures of approximately the same size as the broad end of HIV-1 conical capsids were observed at the plasma membranes of treated cells only, possibly indicating an arrest of the budding process. Corresponding tripeptides with nonamidated carboxyl termini were not biologically active and did not interact with p24.