Spermine and spermidine bind CXCR4 and inhibit CXCR4- but not CCR5-tropic HIV-1 infection - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Science Advances Année : 2023

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 Stürzel
  • Fonction : Auteur
Yasser Ruiz-Blanco
Yasser Almeida-Hernández
Armando Rodriguez-Alfonso
Dominique Cathelin
Birgit Caspar
  • Fonction : Auteur
Sophie Sayettat
Nassima Bekaddour
Kanika Vanshylla
Franziska Kleipass
Sebastian Wiese
  • Fonction : Auteur
Ludger Ständker
  • Fonction : Auteur
Florian Klein
Bernard Lagane
Arnaud Boonen
Dominique Schols
Serge Benichou
Elsa Sanchez-Garcia

Résumé

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.
Fichier principal
Vignette du fichier
sciadv.adf8251.pdf (1.27 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-04198762 , version 1 (23-10-2023)

Identifiants

Citer

Mirja Harms, Nikaïa Smith, Mingyu Han, Rüdiger Groß, Pascal von Maltitz, et al.. Spermine and spermidine bind CXCR4 and inhibit CXCR4- but not CCR5-tropic HIV-1 infection. Science Advances , 2023, 9 (27), pp.eadf8251. ⟨10.1126/sciadv.adf8251⟩. ⟨hal-04198762⟩
14 Consultations
18 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More