Spermine and spermidine bind CXCR4 and inhibit CXCR4- but not CCR5-tropic HIV-1 infection
Mirja Harms, Nikaïa Smith, Mingyu Han, Rüdiger Groß, Pascal von Maltitz, Christina M. Stürzel, Yasser B. Ruiz‐Blanco, Yasser Almeida‐Hernández, Armando Rodríguez, 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 Bénichou, Elsa Sánchez‐García, Jean‐Philippe Herbeuval, Jan Münch
Abstract
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.