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

我们最近的研究表明，精液——HIV/AIDS的主要传播媒介——含有淀粉样肽聚集体，可显著增强HIV-1感染。这些淀粉样蛋白结构是由大量精液标志物前列腺酸性磷酸酶的自然片段形成的，被称为“精液源性病毒感染增强子”（SEVI）。SEVI捕获HIV-1病毒粒子并促进病毒粒子附着于细胞，从而将感染性病毒滴度提高几个数量级。我们的观察结果表明，sevi介导的HIV-1感染增强可能在HIV/AIDS在人群中的传播中起关键作用。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，我们建议将我们在HIV/AIDS和淀粉样蛋白方面的互补专业知识结合起来。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，并可能导致预防艾滋病的新方法。

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.