HIV-1 enhancing effect of prostatic acid phosphatase peptides is reduced in human seminal plasma.

HIV-1 enhancing effect of prostatic acid phosphatase peptides is reduced in human seminal plasma.
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DOI:
10.1371/journal.pone.0016285
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发表时间:
2011-01-20
期刊:
影响因子:
3.7
通讯作者:
Cole AM
Cole AM
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Martellini JA;Cole AL;Svoboda P;Stuchlik O;Chen LM;Chai KX;Gangrade BK;Sørensen OE;Pohl J;Cole AM

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我们最近报道说,人类精浆(SP)的先天抗菌成分可以抑制 HIV-1 感染。相反,据报道,来自 SP 衍生的前列腺酸性磷酸酶 (PAP) 的天然肽片段可形成称为“SEVI”的淀粉样原纤维,并在体外增强 HIV-1 感染。为了了解这种前病毒效应的生物学后果,我们在人类 SP 存在的情况下扩展了这些研究。搅拌 PAP 衍生肽以形成 SEVI,并在存在或不存在 SP 的情况下孵育。虽然 PAP 衍生肽和 SEVI 单独具有前病毒活性,但在几种不同的抗 HIV-1 测定中,1% SP 的存在消除了它们的前病毒活性。 SP 的抗 HIV-1 活性具有浓度依赖性,并在过滤后降低。与稀释的 SP 一起孵育的 PAP 肽和 SEVI 的超生理浓度在数小时内降解,SP 在高达 1∶200 的稀释度下表现出蛋白水解活性。两种主要的 SP 蛋白酶、前列腺特异性抗原 (PSA) 和 matriptase 的亚生理浓度可能会降低 PAP 肽和 SEVI 的生理和超生理浓度。虽然人 SP 是一种复杂的生物液体,含有抗病毒因子和前病毒因子,但我们的结果表明,PAP 肽和 SEVI 可能会受到天然存在的蛋白水解成分的影响,从而降低其前病毒活性。
We recently reported that HIV-1 infection can be inhibited by innate antimicrobial components of human seminal plasma (SP). Conversely, naturally occurring peptidic fragments from the SP-derived prostatic acid phosphatase (PAP) have been reported to form amyloid fibrils called “SEVI” and enhance HIV-1 infection in vitro. In order to understand the biological consequence of this proviral effect, we extended these studies in the presence of human SP. PAP-derived peptides were agitated to form SEVI and incubated in the presence or absence of SP. While PAP-derived peptides and SEVI alone were proviral, the presence of 1% SP ablated their proviral activity in several different anti-HIV-1 assays. The anti-HIV-1 activity of SP was concentration dependent and was reduced following filtration. Supraphysiological concentrations of PAP peptides and SEVI incubated with diluted SP were degraded within hours, with SP exhibiting proteolytic activity at dilutions as high as 1∶200. Sub-physiological concentrations of two prominent proteases of SP, prostate-specific antigen (PSA) and matriptase, could degrade physiological and supraphysiological concentrations of PAP peptides and SEVI. While human SP is a complex biological fluid, containing both antiviral and proviral factors, our results suggest that PAP peptides and SEVI may be subject to naturally occurring proteolytic components capable of reducing their proviral activity.
DOI: 10.1186/1742-4690-7-55
发表时间: 2010-06-23
期刊: Retrovirology
影响因子: 3.3
作者:
Kim KA;Yolamanova M;Zirafi O;Roan NR;Staendker L;Forssmann WG;Burgener A;Dejucq-Rainsford N;Hahn BH;Shaw GM;Greene WC;Kirchhoff F;Münch J
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影响因子: 4.8
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发表时间: 2002-01-01
期刊: EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子: --
作者:
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DOI: 10.1172/jci112120
发表时间: 1985-01-01
影响因子: 15.9
作者:
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DOI: 10.4049/jimmunol.181.5.3413
发表时间: 2008-09-01
影响因子: 4.4
作者:
Edstrom, Anneli M. L.;Malm, Johan;Frohm, Birgitta;Martellini, Julie A.;Giwercman, Aleksander;Morgelin, Matthias;Cole, Alexander M.;Sorensen, Ole E.
通讯作者: Sorensen, Ole E.