候选型杀微生物剂在补体病毒调理后对 HIV-1 感染早期步骤的差异活性。

Differential activity of candidate microbicides against early steps of HIV-1 infection upon complement virus opsonization.

机构信息

Université Paris Descartes (Paris V), Laboratoire de Virologie, Hôpital Européen Georges Pompidou, Paris, France.

出版信息

AIDS Res Ther. 2010 Jun 14;7:16. doi: 10.1186/1742-6405-7-16.

DOI:10.1186/1742-6405-7-16

PMID:20546571

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2895573/

Abstract

BACKGROUND

HIV-1 in genital secretions may be opsonized by several molecules including complement components. Opsonized HIV-1 by complement enhances the infection of various mucosal target cells, such as dendritic cells (DC) and epithelial cells.

RESULTS

We herein evaluated the effect of HIV-1 complement opsonization on microbicide candidates' activity, by using three in vitro mucosal models: CCR5-tropic HIV-1JR-CSF transcytosis through epithelial cells, HIV-1JR-CSF attachment on immature monocyte-derived dendritic cells (iMDDC), and infectivity of iMDDC by CCR5-tropic HIV-1BaL and CXCR4-tropic HIV-1NDK. A panel of 10 microbicide candidates [T20, CADA, lectines HHA & GNA, PVAS, human lactoferrin, and monoclonal antibodies IgG1B12, 12G5, 2G12 and 2F5], were investigated using cell-free unopsonized or opsonized HIV-1 by complements. Only HHA and PVAS were able to inhibit HIV trancytosis. Upon opsonization, transcytosis was affected only by HHA, HIV-1 adsorption on iMDDC by four molecules (lactoferrin, IgG1B12, IgG2G5, IgG2G12), and replication in iMDDC of HIV-1BaL by five molecules (lactoferrin, CADA, T20, IgG1B12, IgG2F5) and of HIV-1NDK by two molecules (lactoferrin, IgG12G5).

CONCLUSION

These observations demonstrate that HIV-1 opsonization by complements may modulate in vitro the efficiency of candidate microbicides to inhibit HIV-1 infection of mucosal target cells, as well as its crossing through mucosa.

摘要

背景

艾滋病毒-1 在生殖分泌物中可能被几种分子包裹，包括补体成分。补体包裹的艾滋病毒-1 增强了各种黏膜靶细胞（如树突状细胞[DC]和上皮细胞）的感染。

结果

我们在此通过三种体外黏膜模型评估了 HIV-1 补体包裹对杀微生物候选物活性的影响：CCR5 嗜性 HIV-1JR-CSF 通过上皮细胞的转胞吞作用、未成熟单核细胞衍生的树突状细胞（iMDDC）上的 HIV-1JR-CSF 附着以及 CCR5 嗜性 HIV-1BaL 和 CXCR4 嗜性 HIV-1NDK 对 iMDDC 的感染性。我们使用 10 种杀微生物候选物[T20、CADA、凝集素 HHA 和 GNA、PVAS、人乳铁蛋白和单克隆抗体 IgG1B12、12G5、2G12 和 2F5]组成的面板，对无细胞包裹或补体包裹的未感染 HIV-1 进行了研究。只有 HHA 和 PVAS 能够抑制 HIV 转胞吞作用。在包裹后，只有 HHA 会影响转胞吞作用，四种分子（乳铁蛋白、IgG1B12、IgG2G5 和 IgG2G12）会影响 iMDDC 上的 HIV-1 吸附，五种分子（乳铁蛋白、CADA、T20、IgG1B12 和 IgG2F5）会影响 HIV-1BaL 在 iMDDC 中的复制，两种分子（乳铁蛋白和 IgG12G5）会影响 HIV-1NDK 在 iMDDC 中的复制。