Spermine and spermidine bind CXCR4 and inhibit CXCR4- but not CCR5-tropic HIV-1 infection.
Journal
Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440
Informations de publication
Date de publication:
07 07 2023
07 07 2023
Historique:
medline:
7
7
2023
pubmed:
5
7
2023
entrez:
5
7
2023
Statut:
ppublish
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.
Identifiants
pubmed: 37406129
doi: 10.1126/sciadv.adf8251
pmc: PMC10321752
doi:
Substances chimiques
Spermidine
U87FK77H25
Spermine
2FZ7Y3VOQX
CXCR4 protein, human
0
Receptors, CXCR4
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
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