Cationic polypeptides contribute to the anti-HIV-1 activity of human seminal plasma
Cationic polypeptides contribute to the anti-HIV-1 activity of human seminal plasma
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DOI：
10.1096/fj.09-131961
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发表时间：
2009-10-01
期刊：
影响因子：
4.8
通讯作者：
Cole, Alexander M.
中科院分区：
文献类型：
--
作者：
Martellini, Julie A.;Cole, Amy L.;Cole, Alexander M.
生殖道的粘液表面及其分泌物在预防HIV-1的性传播方面具有重要作用。在目前的研究中，大多数人精浆（SP）的内在抗HIV-1活性被确定为驻留在阳离子多肽部分。利用荧光素酶报告细胞和淋巴细胞的抗病毒测定揭示了整个SP预防HIV-1感染的能力，即使SP稀释3200倍。随后通过连续流酸-尿素（Au）-PAGE和抗病毒测试进行分级分离，结果显示SP内的阳离子多肽负责大部分抗HIV-1活性。一个蛋白质组学的方法被用来解决和确定52个个人的阳离子多肽，有助于总抗HIV-1活性的SP。一个肽片段的semenogelin I，称为SG-1，从SP纯化的多步色谱法，蛋白质测序，并确定表现出抗HIV-1活性对HIV-1。抗HIV-1活性是短暂的，因为整个SP孵育延长的时间间隔表现出抗HIV-1活性的成比例降低，这直接归因于精液凝固蛋白I肽的降解。总的来说，这些结果表明SP的阳离子多肽级分具有抗HIV-1的活性，并且精液凝胶衍生肽有助于SP的内在抗HIV-1活性。Martellini，J. A.，科尔。C.的方法，Venkataraman，N.，Quinn，G.一、Svoboda，P.，流氓，B。K.，Pohl，J.，索伦森岛E、科尔，A. M.阳离子多肽有助于人精浆的抗HIV-1活性。FASEB J.23，3609 - 3618（2009）. www.fasebj.org
Mucosal surfaces of the reproductive tract as well as their secretions have important roles in preventing sexual transmission of HIV-1. In the current study, the majority of the intrinsic anti-HIV-1 activity of human seminal plasma (SP) was determined to reside in the cationic polypeptide fraction. Antiviral assays utilizing luciferase reporter cells and lymphocytic cells revealed the ability of whole SP to prevent HIV-1 infection, even when SP was diluted 3200-fold. Subsequent fractionation by continuous flow acid-urea (AU)-PAGE and antiviral testing revealed that cationic polypeptides within SP were responsible for the majority of anti-HIV-1 activity. A proteomic approach was utilized to resolve and identify 52 individual cationic polypeptides that contribute to the aggregate anti-HIV-1 activity of SP. One peptide fragment of semenogelin I, termed SG-1, was purified from SP by a multistep chromatographic approach, protein sequenced, and determined to exhibit anti-HIV-1 activity against HIV-1. Anti-HIV-1 activity was transient, as whole SP incubated for prolonged time intervals exhibited a proportional decrease in anti-HIV-1 activity that was directly attributed to the degradation of semenogelin I peptides. Collectively, these results indicate that the cationic polypeptide fraction of SP is active against HIV-1, and that semenogelin-derived peptides contribute to the intrinsic anti-HIV-1 activity of SP.-Martellini, J. A., Cole, A. C., Venkataraman, N., Quinn, G. A., Svoboda, P., Gangrade, B. K., Pohl, J., Sorensen, O. E., Cole, A. M. Cationic polypeptides contribute to the anti-HIV-1 activity of human seminal plasma. FASEB J. 23, 3609-3618 (2009). www.fasebj.org