Mechanism and Structural Basis of SEVI-Mediated Enhancement of HIV Infection

SEVI介导的HIV感染增强机制和结构基础

• 批准号: 193603148
• 负责人: Professor Dr. Marcus Fändrich
• 金额: --
• 依托单位: Institut für Molekulare Virologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2011
• 资助国家: 德国
• 起止时间: 2010-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/193603148?language=en
• 关键词: Mechanism; Structural; Basis; SEVI; Mediated

We have recently shown that semen - the major vehicle for the transmission of HIV/AIDS - contains amyloid peptide aggregates that drastically enhance HIV-1 infection. These amyloid structures are formed by naturally occurring fragments of the abundant semen marker prostatic acid phosphatase, and were termed ‘Semen-derived Enhancer of Virus Infection’ (SEVI). SEVI captures HIV-1 virions and promotes virion attachment to the cell, thereby increasing the infectious virus titer by several orders of magnitude. Our observations suggest that SEVI-mediated enhancement of HIV-1 infection may play a key role in the dissemination of HIV/AIDS in the human population. To determine the mechanisms of SEVI- and semenmediated enhancement of HIV infection and to explore how the virus enhancing effect of semen can be blocked, we here propose to combine our complementary expertise in HIV/AIDS and amyloids. Our results will provide novel insights into the mechanisms of sexual transmission of HIV/AIDS and may lead to new approaches to prevent it.

我们最近发现，精液-艾滋病毒/艾滋病传播的主要载体-含有淀粉样肽聚集体，大大增强了HIV-1感染。这些淀粉样结构是由丰富的精液标志物前列腺酸性磷酸酶的天然片段形成的，并被称为“精液衍生的病毒感染增强剂”（SEVI）。SEVI捕获HIV-1病毒粒子并促进病毒粒子附着于细胞，从而使感染性病毒滴度增加几个数量级。我们的观察表明，SEVI介导的HIV-1感染的增强可能在人群中传播HIV/AIDS中发挥关键作用。为了确定SEVI和精液介导的增强HIV感染的机制，并探索如何阻断精液的病毒增强作用，我们在这里提出联合收割机结合我们在HIV/AIDS和淀粉样蛋白方面的互补专业知识。我们的研究结果将为艾滋病毒/艾滋病的性传播机制提供新的见解，并可能导致新的方法来预防它。

项目成果

Naturally Occurring Fragments from Two Distinct Regions of the Prostatic Acid Phosphatase Form Amyloidogenic Enhancers of HIV Infection

• DOI: 10.1128/jvi.06121-11
• 发表时间: 2012-01-01
• 期刊: JOURNAL OF VIROLOGY
• 影响因子: 5.4
• 作者: Arnold, Franziska;Schnell, Jacqueline;Muench, Jan
• 通讯作者: Muench, Jan

Liquefaction of Semen Generates and Later Degrades a Conserved Semenogelin Peptide That Enhances HIV Infection

• DOI: 10.1128/jvi.00269-14
• 发表时间: 2014-07-01
• 期刊: JOURNAL OF VIROLOGY
• 影响因子: 5.4
• 作者: Roan, Nadia R.;Liu, Haichuan;Greene, Warner C.
• 通讯作者: Greene, Warner C.

Effect of semen and seminal amyloid on vaginal transmission of simian immunodeficiency virus

• DOI: 10.1186/1742-4690-10-148
• 发表时间: 2013-12-05
• 期刊: RETROVIROLOGY
• 影响因子: 3.3
• 作者: Muench, Jan;Sauermann, Ulrike;Kirchhoff, Frank
• 通讯作者: Kirchhoff, Frank