Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
CNRS UMR-8601, Université Paris Cité, 75006 Paris, France.
Sci Adv. 2023 Jul 7;9(27):eadf8251. doi: 10.1126/sciadv.adf8251. Epub 2023 Jul 5.
Semen is an important vector for sexual HIV-1 transmission. Although CXCR4-tropic (X4) HIV-1 may be present in semen, almost exclusively CCR5-tropic (R5) HIV-1 causes systemic infection after sexual intercourse. To identify factors that may limit sexual X4-HIV-1 transmission, we generated a seminal fluid-derived compound library and screened it for antiviral agents. We identified four adjacent fractions that blocked X4-HIV-1 but not R5-HIV-1 and found that they all contained spermine and spermidine, abundant polyamines in semen. We showed that spermine, which is present in semen at concentrations up to 14 mM, binds CXCR4 and selectively inhibits cell-free and cell-associated X4-HIV-1 infection of cell lines and primary target cells at micromolar concentrations. Our findings suggest that seminal spermine restricts sexual X4-HIV-1 transmission.
精液是 HIV-1 性传播的重要载体。虽然精液中可能存在 CXCR4 嗜性（X4）HIV-1，但几乎完全是 CCR5 嗜性（R5）HIV-1 在性交后引起全身感染。为了确定可能限制性 X4-HIV-1 传播的因素，我们生成了一个精液衍生的化合物文库，并对其进行了抗病毒药物筛选。我们发现了四个相邻的抑制 X4-HIV-1 的分数，而不抑制 R5-HIV-1，并且发现它们都含有精胺和亚精胺，这是精液中的丰富多胺。我们表明，精胺在精液中的浓度高达 14mM，它可以结合 CXCR4，并以微摩尔浓度选择性地抑制无细胞和细胞相关的 X4-HIV-1 感染细胞系和原代靶细胞。我们的研究结果表明，精液中的精胺限制了性 X4-HIV-1 的传播。
