A cinnamon-derived procyanidin compound displays anti-HIV-1 activity by blocking heparan sulfate- and co-receptor- binding sites on gp120 and reverses T cell exhaustion via impeding Tim-3 and PD-1 upregulation

Bridgette Janine Connell, Sui Yuan Chang, Ekambaranellore Prakash, Rahima Yousfi, Viswaraman Mohan, Wilfried Posch, Doris Wilflingseder, Christiane Moog, Eiichi N. Kodama, Pascal Clayette, Hugues Lortat-Jacob

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Amongst the many strategies aiming at inhibiting HIV-1 infection, blocking viral entry has been recently recognized as a very promising approach. Using diverse in vitro models and a broad range of HIV-1 primary patient isolates, we report here that IND02, a type A procyanidin polyphenol extracted from cinnamon, that features trimeric and pentameric forms displays an anti-HIV-1 activity against CXCR4 and CCR5 viruses with 1-7 μM ED50 for the trimer. Competition experiments, using a surface plasmon resonance-based binding assay, revealed that IND02 inhibited envelope binding to CD4 and heparan sulphate (HS) as well as to an antibody (mAb 17b) directed against the gp120 co-receptor binding site with an IC50 in the low μM range. IND02 has thus the remarkable property of simultaneously blocking gp120 binding to its major host cell surface counterparts. Additionally, the IND02-trimer impeded up-regulation of the inhibitory receptors Tim-3 and PD-1 on CD4+ and CD8+ cells, thereby demonstrating its beneficial effect by limiting T cell exhaustion. Among naturally derived products significantly inhibiting HIV-1, the IND02-trimer is the first component demonstrating an entry inhibition property through binding to the viral envelope glycoprotein. These data suggest that cinnamon, a widely consumed spice, could represent a novel and promising candidate for a cost-effective, natural entry inhibitor for HIV-1 which can also down-modulate T cell exhaustion markers Tim-3 and PD-1.

Original languageEnglish
Article numbere0165386
JournalPloS one
Volume11
Issue number10
DOIs
Publication statusPublished - 2016 Oct

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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