Cargando…
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...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
American Association for the Advancement of Science
2023
|
| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10321752/ https://www.ncbi.nlm.nih.gov/pubmed/37406129 http://dx.doi.org/10.1126/sciadv.adf8251 |
| _version_ | 1785068679491223552 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Harms, Mirja |
| collection | PubMed |
| description | 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. |
| format | Online Article Text |
| id | pubmed-10321752 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2023 |
| publisher | American Association for the Advancement of Science |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-103217522023-07-06 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 Sci Adv Biomedicine and Life Sciences 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. American Association for the Advancement of Science 2023-07-05 /pmc/articles/PMC10321752/ /pubmed/37406129 http://dx.doi.org/10.1126/sciadv.adf8251 Text en Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
| spellingShingle | Biomedicine and Life Sciences 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 Spermine and spermidine bind CXCR4 and inhibit CXCR4- but not CCR5-tropic HIV-1 infection |
| title | Spermine and spermidine bind CXCR4 and inhibit CXCR4- but not CCR5-tropic HIV-1 infection |
| title_full | Spermine and spermidine bind CXCR4 and inhibit CXCR4- but not CCR5-tropic HIV-1 infection |
| title_fullStr | Spermine and spermidine bind CXCR4 and inhibit CXCR4- but not CCR5-tropic HIV-1 infection |
| title_full_unstemmed | Spermine and spermidine bind CXCR4 and inhibit CXCR4- but not CCR5-tropic HIV-1 infection |
| title_short | Spermine and spermidine bind CXCR4 and inhibit CXCR4- but not CCR5-tropic HIV-1 infection |
| title_sort | spermine and spermidine bind cxcr4 and inhibit cxcr4- but not ccr5-tropic hiv-1 infection |
| topic | Biomedicine and Life Sciences |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10321752/ https://www.ncbi.nlm.nih.gov/pubmed/37406129 http://dx.doi.org/10.1126/sciadv.adf8251 |
| work_keys_str_mv | AT harmsmirja spermineandspermidinebindcxcr4andinhibitcxcr4butnotccr5tropichiv1infection AT smithnikaia spermineandspermidinebindcxcr4andinhibitcxcr4butnotccr5tropichiv1infection AT hanmingyu spermineandspermidinebindcxcr4andinhibitcxcr4butnotccr5tropichiv1infection AT großrudiger spermineandspermidinebindcxcr4andinhibitcxcr4butnotccr5tropichiv1infection AT vonmaltitzpascal spermineandspermidinebindcxcr4andinhibitcxcr4butnotccr5tropichiv1infection AT sturzelchristina spermineandspermidinebindcxcr4andinhibitcxcr4butnotccr5tropichiv1infection AT ruizblancoyasserb spermineandspermidinebindcxcr4andinhibitcxcr4butnotccr5tropichiv1infection AT almeidahernandezyasser spermineandspermidinebindcxcr4andinhibitcxcr4butnotccr5tropichiv1infection AT rodriguezalfonsoarmando spermineandspermidinebindcxcr4andinhibitcxcr4butnotccr5tropichiv1infection AT cathelindominique spermineandspermidinebindcxcr4andinhibitcxcr4butnotccr5tropichiv1infection AT casparbirgit spermineandspermidinebindcxcr4andinhibitcxcr4butnotccr5tropichiv1infection AT taharbouceba spermineandspermidinebindcxcr4andinhibitcxcr4butnotccr5tropichiv1infection AT sayettatsophie spermineandspermidinebindcxcr4andinhibitcxcr4butnotccr5tropichiv1infection AT bekaddournassima spermineandspermidinebindcxcr4andinhibitcxcr4butnotccr5tropichiv1infection AT vanshyllakanika spermineandspermidinebindcxcr4andinhibitcxcr4butnotccr5tropichiv1infection AT kleipassfranziska spermineandspermidinebindcxcr4andinhibitcxcr4butnotccr5tropichiv1infection AT wiesesebastian spermineandspermidinebindcxcr4andinhibitcxcr4butnotccr5tropichiv1infection AT standkerludger spermineandspermidinebindcxcr4andinhibitcxcr4butnotccr5tropichiv1infection AT kleinflorian spermineandspermidinebindcxcr4andinhibitcxcr4butnotccr5tropichiv1infection AT laganebernard spermineandspermidinebindcxcr4andinhibitcxcr4butnotccr5tropichiv1infection AT boonenarnaud spermineandspermidinebindcxcr4andinhibitcxcr4butnotccr5tropichiv1infection AT scholsdominique spermineandspermidinebindcxcr4andinhibitcxcr4butnotccr5tropichiv1infection AT benichouserge spermineandspermidinebindcxcr4andinhibitcxcr4butnotccr5tropichiv1infection AT sanchezgarciaelsa spermineandspermidinebindcxcr4andinhibitcxcr4butnotccr5tropichiv1infection AT herbeuvaljeanphilippe spermineandspermidinebindcxcr4andinhibitcxcr4butnotccr5tropichiv1infection AT munchjan spermineandspermidinebindcxcr4andinhibitcxcr4butnotccr5tropichiv1infection |