Institute of Molecular Virology, University Hospital Ulm, 89081 Ulm, Germany.
Retrovirology. 2010 Jun 23;7:55. doi: 10.1186/1742-4690-7-55.
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.
HIV-1 通常在精液存在的情况下传播。我们已经表明,精液会增强 HIV-1 的感染,并含有前列腺酸性磷酸酶(PAP)的片段,形成称为 SEVI(精液衍生的病毒感染增强子)的淀粉样聚集物,促进病毒粒子附着到靶细胞上。然而,尽管它对 HIV-1 在全球的传播至关重要,但精液对病毒感染的影响仍存在争议。
在这里,我们建立了方法,可以通过最小化其细胞毒性作用并部分再现性传播过程中遇到的条件来对精液进行有意义的分析。我们表明,精液可迅速有效地增强 HIV-1、HIV-2 和 SIV 的感染性。这种增强作用独立于病毒基因型和核心受体嗜性以及病毒产生者和靶细胞类型。在酸性 pH 条件下和存在阴道液的情况下,也观察到精液介导的 HIV-1 感染增强。我们进一步表明,精液增强 HIV-1 感染的效力取决于供体,并与 SEVI 的水平相关。
我们的结果表明,精液强烈增强了 HIV-1 和其他灵长类慢病毒的感染性,而 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,并且向杀微生物剂中添加 SEVI 抑制剂可能会提高它们的功效。