精液衍生的淀粉样纤维显著增强HIV感染。

Semen-derived amyloid fibrils drastically enhance HIV infection.

作者信息

Münch Jan, Rücker Elke, Ständker Ludger, Adermann Knut, Goffinet Christine, Schindler Michael, Wildum Steffen, Chinnadurai Raghavan, Rajan Devi, Specht Anke, Giménez-Gallego Guillermo, Sánchez Pedro Cuevas, Fowler Douglas M, Koulov Atanas, Kelly Jeffery W, Mothes Walther, Grivel Jean-Charles, Margolis Leonid, Keppler Oliver T, Forssmann Wolf-Georg, Kirchhoff Frank

机构信息

Institute of Virology, University Clinic of Ulm, 89081 Ulm, Germany.

出版信息

Cell. 2007 Dec 14;131(6):1059-71. doi: 10.1016/j.cell.2007.10.014.

DOI:10.1016/j.cell.2007.10.014

PMID:18083097

Abstract

Sexual intercourse is the major route of HIV transmission. To identify endogenous factors that affect the efficiency of sexual viral transmission, we screened a complex peptide/protein library derived from human semen. We show that naturally occurring fragments of the abundant semen marker prostatic acidic phosphatase (PAP) form amyloid fibrils. These fibrils, termed Semen-derived Enhancer of Virus Infection (SEVI), capture HIV virions and promote their attachment to target cells, thereby enhancing the infectious virus titer by several orders of magnitude. Physiological concentrations of SEVI amplified HIV infection of T cells, macrophages, ex vivo human tonsillar tissues, and transgenic rats in vivo, as well as trans-HIV infection of T cells by dendritic or epithelial cells. Amyloidogenic PAP fragments are abundant in seminal fluid and boost semen-mediated enhancement of HIV infection. Thus, they may play an important role in sexual transmission of HIV and could represent new targets for its prevention.

摘要

性交是艾滋病毒传播的主要途径。为了确定影响性传播病毒效率的内源性因素，我们筛选了一个源自人类精液的复合肽/蛋白质文库。我们发现，精液中丰富的标志物前列腺酸性磷酸酶（PAP）的天然片段会形成淀粉样纤维。这些纤维被称为精液衍生病毒感染增强剂（SEVI），它能捕获艾滋病毒颗粒并促进其与靶细胞的附着，从而将感染性病毒滴度提高几个数量级。生理浓度的SEVI可在体外增强艾滋病毒对T细胞、巨噬细胞、人扁桃体组织的感染，在体内增强对转基因大鼠的感染，以及通过树突状细胞或上皮细胞实现T细胞的跨艾滋病毒感染。淀粉样生成性PAP片段在精液中含量丰富，并能增强精液介导的艾滋病毒感染。因此，它们可能在艾滋病毒的性传播中发挥重要作用，并可能成为预防艾滋病毒的新靶点。