Semen-mediated enhancement of HIV infection is donor-dependent and correlates with the levels of SEVI.

Semen-mediated enhancement of HIV infection is donor-dependent and correlates with the levels of SEVI.
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DOI:
10.1186/1742-4690-7-55
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发表时间:
2010-06-23
期刊:
影响因子:
3.3
通讯作者:
Münch J
Münch J
中科院分区:
医学2区
文献类型:
--
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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HIV-1通常在精液存在的情况下传播。我们已经证明,精液促进HIV-1感染,并含有前列腺酸性磷酸酶(PAP)片段,形成名为SEVI(精液来源的病毒感染增强剂)的淀粉样聚集体,促进病毒粒子与靶细胞的附着。然而,尽管精液对HIV-1在全球传播具有重要意义,但精液对病毒感染的影响仍存在争议。在这里,我们建立了一些方法,通过将精液的细胞毒性作用降至最低,并部分概括了在性传播HIV-1期间遇到的情况,从而允许对精液进行有意义的分析。我们发现精液可以快速有效地增强HIV-1、HIV-2和SIV的传染性。这种增强与病毒的基因型和共同受体的趋向性以及病毒的产生细胞和靶细胞类型无关。在酸性pH条件下和阴道液存在的情况下,也观察到精液介导的HIV-1感染的增强。我们进一步证明,精液促进HIV-1感染的效力依赖于捐赠者,并与SEVI水平相关。我们的结果表明,精液强烈地增强了HIV-1和其他灵长类慢病毒的传染性,SEVI有助于这种作用。因此,SEVI可能在HIV-1的性传播中发挥重要作用,在杀微生物剂中添加SEVI抑制剂可能会提高其疗效。
HIV-1 is usually transmitted in the presence of semen. We have shown that semen boosts HIV-1 infection and contains fragments of prostatic acid phosphatase (PAP) forming amyloid aggregates termed SEVI (semen-derived enhancer of viral infection) that promote virion attachment to target cells. Despite its importance for the global spread of HIV-1, however, the effect of semen on virus infection is controversial. Here, we established methods allowing the meaningful analysis of semen by minimizing its cytotoxic effects and partly recapitulating the conditions encountered during sexual HIV-1 transmission. We show that semen rapidly and effectively enhances the infectivity of HIV-1, HIV-2, and SIV. This enhancement occurs independently of the viral genotype and coreceptor tropism as well as the virus producer and target cell type. Semen-mediated enhancement of HIV-1 infection was also observed under acidic pH conditions and in the presence of vaginal fluid. We further show that the potency of semen in boosting HIV-1 infection is donor dependent and correlates with the levels of SEVI. Our results show that semen strongly enhances the infectivity of HIV-1 and other primate lentiviruses and that SEVI contributes to this effect. Thus, SEVI may play an important role in the sexual transmission of HIV-1 and addition of SEVI inhibitors to microbicides may improve their efficacy.
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