Procyanidin trimer C1 derived from Theobroma cacao reactivates latent human immunodeficiency virus type 1 provirus

Biochemical and Biophysical Research Communications
Takanori HoriShoji Yamaoka

Abstract

Despite remarkable advances in combination antiretroviral therapy (cART), human immunodeficiency virus type 1 (HIV-1) infection remains incurable due to the incomplete elimination of the replication-competent virus, which persists in latent reservoirs. Strategies for targeting HIV reservoirs for eradication that involves reactivation of latent proviruses while protecting uninfected cells by cART are urgently needed for cure of HIV infection. We screened medicinal plant extracts for compounds that could reactivate the latent HIV-1 provirus and identified a procyanidin trimer C1 derived from Theobroma cacao as a potent activator of the provirus in human T cells latently infected with HIV-1. This reactivation largely depends on the NF-κB and MAPK signaling pathways because either overexpression of a super-repressor form of IκBα or pretreatment with a MEK inhibitor U0126 diminished provirus reactivation by C1. A pan-PKC inhibitor significantly blocked the phorbol ester-induced but not the C1-induced HIV-1 reactivation. Although C1-induced viral gene expression persisted for as long as 48 h post-stimulation, NF-κB-dependent transcription peaked at 12 h post-stimulation and then quickly declined, suggesting Tat-mediated self-sustainm...Continue Reading

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Citations

Jan 6, 2016·The Journal of Clinical Investigation·Daniele C CaryB Matija Peterlin
Dec 16, 2016·PloS One·Daniele C CaryB Matija Peterlin
Dec 12, 2017·AIDS Research and Human Retroviruses·Daniele C Cary, B Matija Peterlin
Jun 16, 2016·F1000Research·Daniele C Cary, B Matija Peterlin
Aug 27, 2017·Scientific Reports·Pengfei WangHuanzhang Zhu
Jul 15, 2017·AIDS Research and Therapy·Alexander KwartengGodwin Kwakye-Nuako
Nov 14, 2020·Viruses·Koh Fujinaga, Daniele C Cary
Jun 3, 2021·Viruses·Maria Musarra-PizzoMaria Teresa Sciortino

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