Spermine and spermidine bind CXCR4 and inhibit CXCR4- but not CCR5-tropic HIV-1 infection-Reference-Cited by-同舟云学术

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

Published:2023-07-07 Issue:27 Volume:9 Page:
ISSN:2375-2548
Container-title:Science Advances
language:en
Short-container-title:Sci. Adv.

Author:

Harms Mirja¹^ORCID,Smith Nikaïa¹²³^ORCID,Han Mingyu³^ORCID,Groß Rüdiger¹^ORCID,von Maltitz Pascal¹^ORCID,Stürzel Christina¹,Ruiz-Blanco Yasser B.⁴^ORCID,Almeida-Hernández Yasser⁵^ORCID,Rodriguez-Alfonso Armando⁶⁷^ORCID,Cathelin Dominique²⁸^ORCID,Caspar Birgit²⁸,Tahar Bouceba⁹,Sayettat Sophie³^ORCID,Bekaddour Nassima²⁸^ORCID,Vanshylla Kanika¹⁰^ORCID,Kleipass Franziska¹⁰^ORCID,Wiese Sebastian⁷,Ständker Ludger⁶,Klein Florian¹⁰¹¹¹²^ORCID,Lagane Bernard¹³^ORCID,Boonen Arnaud¹⁴^ORCID,Schols Dominique¹⁴^ORCID,Benichou Serge³^ORCID,Sanchez-Garcia Elsa⁴⁵^ORCID,Herbeuval Jean-Philippe²⁸^ORCID,Münch Jan¹^ORCID

Affiliation:

1. Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.

2. CNRS UMR-8601, Université Paris Cité, 75006 Paris, France.

3. Institut Cochin, Inserm U1016, CNRS UMR8104, Université Paris-Cité, 75014 Paris, France.

4. Computational Biochemistry, Center of Medical Biotechnology, University of Duisburg-Essen, Universitätsstr. 2, 45141 Essen, Germany.

5. Computational Bioengineering, Department of Biochemical and Chemical Engineering, Emil-Figge Str. 66., 44227 Dortmund, Germany.

6. Core Facility Functional Peptidomics, Ulm University Medical Center, 89081 Ulm, Germany.

7. Core Unit Mass Spectrometry and Proteomics, Ulm University, 89081 Ulm, Germany.

8. Chemistry and Biology, Modeling and Immunology for Therapy (CBMIT), Paris, France.

9. Sorbonne University, CNRS, Institut de Biologie Paris-Seine (IBPS), Protein Engineering Platform, Molecular Interaction Service, F-75252 Paris, France.

10. Laboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.

11. German Center for Infection Research (DZIF), Partner site Bonn-Cologne, 50937 Cologne, Germany.

12. Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, Germany.

13. Infinity, Université de Toulouse, CNRS, INSERM, Toulouse, France.

14. Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, Herestraat 49, P.O. Box 1030, 3000 Leuven, Belgium.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Link

https://www.science.org/doi/pdf/10.1126/sciadv.adf8251

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