Spermine and spermidine bind CXCR4 and inhibit CXCR4- but not CCR5-tropic HIV-1 infection.

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.

Citation

Mirja Harms, Nikaïa Smith, Mingyu Han, Rüdiger Groß, Pascal von Maltitz, Christina Stürzel, Yasser B Ruiz-Blanco, Yasser Almeida-Hernández, Armando Rodriguez-Alfonso, Dominique Cathelin, Birgit Caspar, Bouceba Tahar, Sophie Sayettat, Nassima Bekaddour, Kanika Vanshylla, Franziska Kleipass, Sebastian Wiese, Ludger Ständker, Florian Klein, Bernard Lagane, Arnaud Boonen, Dominique Schols, Serge Benichou, Elsa Sanchez-Garcia, Jean-Philippe Herbeuval, Jan Münch. Spermine and spermidine bind CXCR4 and inhibit CXCR4- but not CCR5-tropic HIV-1 infection. Science advances. 2023 Jul 07;9(27):eadf8251

Mesh Tags

Substances

PMID: 37406129

search → result