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Spermine and spermidine bind CXCR4 and inhibit CXCR4- but not CCR5-tropic HIV-1 infection.
Harms, Mirja; Smith, Nikaïa; Han, Mingyu; Groß, Rüdiger; von Maltitz, Pascal; Stürzel, Christina; Ruiz-Blanco, Yasser B; Almeida-Hernández, Yasser; Rodriguez-Alfonso, Armando; Cathelin, Dominique; Caspar, Birgit; Tahar, Bouceba; Sayettat, Sophie; Bekaddour, Nassima; Vanshylla, Kanika; Kleipass, Franziska; Wiese, Sebastian; Ständker, Ludger; Klein, Florian; Lagane, Bernard; Boonen, Arnaud; Schols, Dominique; Benichou, Serge; Sanchez-Garcia, Elsa; Herbeuval, Jean-Philippe; Münch, Jan.
Affiliation
  • Harms M; Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
  • Smith N; Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
  • Han M; CNRS UMR-8601, Université Paris Cité, 75006 Paris, France.
  • Groß R; Institut Cochin, Inserm U1016, CNRS UMR8104, Université Paris-Cité, 75014 Paris, France.
  • von Maltitz P; Institut Cochin, Inserm U1016, CNRS UMR8104, Université Paris-Cité, 75014 Paris, France.
  • Stürzel C; Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
  • Ruiz-Blanco YB; Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
  • Almeida-Hernández Y; Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
  • Rodriguez-Alfonso A; Computational Biochemistry, Center of Medical Biotechnology, University of Duisburg-Essen, Universitätsstr. 2, 45141 Essen, Germany.
  • Cathelin D; Computational Bioengineering, Department of Biochemical and Chemical Engineering, Emil-Figge Str. 66., 44227 Dortmund, Germany.
  • Caspar B; Core Facility Functional Peptidomics, Ulm University Medical Center, 89081 Ulm, Germany.
  • Tahar B; Core Unit Mass Spectrometry and Proteomics, Ulm University, 89081 Ulm, Germany.
  • Sayettat S; CNRS UMR-8601, Université Paris Cité, 75006 Paris, France.
  • Bekaddour N; Chemistry and Biology, Modeling and Immunology for Therapy (CBMIT), Paris, France.
  • Vanshylla K; CNRS UMR-8601, Université Paris Cité, 75006 Paris, France.
  • Kleipass F; Chemistry and Biology, Modeling and Immunology for Therapy (CBMIT), Paris, France.
  • Wiese S; Sorbonne University, CNRS, Institut de Biologie Paris-Seine (IBPS), Protein Engineering Platform, Molecular Interaction Service, F-75252 Paris, France.
  • Ständker L; Institut Cochin, Inserm U1016, CNRS UMR8104, Université Paris-Cité, 75014 Paris, France.
  • Klein F; CNRS UMR-8601, Université Paris Cité, 75006 Paris, France.
  • Lagane B; Chemistry and Biology, Modeling and Immunology for Therapy (CBMIT), Paris, France.
  • Boonen A; Laboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.
  • Schols D; Laboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.
  • Benichou S; Core Unit Mass Spectrometry and Proteomics, Ulm University, 89081 Ulm, Germany.
  • Sanchez-Garcia E; Core Facility Functional Peptidomics, Ulm University Medical Center, 89081 Ulm, Germany.
  • Herbeuval JP; Laboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.
  • Münch J; German Center for Infection Research (DZIF), Partner site Bonn-Cologne, 50937 Cologne, Germany.
Sci Adv ; 9(27): eadf8251, 2023 07 07.
Article in En | MEDLINE | ID: mdl-37406129
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: HIV Infections / HIV-1 Type of study: Prognostic_studies Limits: Humans Language: En Journal: Sci Adv Year: 2023 Document type: Article Affiliation country: Germany Country of publication: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: HIV Infections / HIV-1 Type of study: Prognostic_studies Limits: Humans Language: En Journal: Sci Adv Year: 2023 Document type: Article Affiliation country: Germany Country of publication: United States