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

Takanori Hori, Jacob Barnor, Tung Nguyen Huu, Osamu Morinaga, Akiko Hamano, Jerry Ndzinu, Angela Frimpong, Keren Minta-Asare, Mildred Amoa-Bosompem, James Brandful, John Odoom, Joseph Bonney, Isaac Tuffour, Baffour Awuah Owusu, Mark Ofosuhene, Philip Atchoglo, Maxwell Sakyiamah, Richard Adegle, Regina Appiah-Opong, William AmpofoKwadwo Koram, Alexander Nyarko, Laud Okine, Dominic Edoh, Alfred Appiah, Takuhiro Uto, Yoshiyuki Yoshinaka, Shin Uota, Yukihiro Shoyama, Shoji Yamaoka

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

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-sustainment of HIV-1 expression. These results suggest that procyanidin C1 trimer is a potential compound for reactivation of latent HIV-1 reservoirs.

Original languageEnglish
Pages (from-to)288-293
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume459
Issue number2
DOIs
Publication statusPublished - 3 Apr 2015
Externally publishedYes

Keywords

  • HIV
  • Latency
  • Procyanidin
  • Reactivation

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