TY - JOUR
T1 - Procyanidin trimer C1 derived from Theobroma cacao reactivates latent human immunodeficiency virus type 1 provirus
AU - Hori, Takanori
AU - Barnor, Jacob
AU - Nguyen Huu, Tung
AU - Morinaga, Osamu
AU - Hamano, Akiko
AU - Ndzinu, Jerry
AU - Frimpong, Angela
AU - Minta-Asare, Keren
AU - Amoa-Bosompem, Mildred
AU - Brandful, James
AU - Odoom, John
AU - Bonney, Joseph
AU - Tuffour, Isaac
AU - Owusu, Baffour Awuah
AU - Ofosuhene, Mark
AU - Atchoglo, Philip
AU - Sakyiamah, Maxwell
AU - Adegle, Richard
AU - Appiah-Opong, Regina
AU - Ampofo, William
AU - Koram, Kwadwo
AU - Nyarko, Alexander
AU - Okine, Laud
AU - Edoh, Dominic
AU - Appiah, Alfred
AU - Uto, Takuhiro
AU - Yoshinaka, Yoshiyuki
AU - Uota, Shin
AU - Shoyama, Yukihiro
AU - Yamaoka, Shoji
N1 - Publisher Copyright:
© 2015 Elsevier Inc. All rights reserved.
PY - 2015/4/3
Y1 - 2015/4/3
N2 - 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.
AB - 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.
KW - HIV
KW - Latency
KW - Procyanidin
KW - Reactivation
UR - http://www.scopus.com/inward/record.url?scp=84925532785&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2015.02.102
DO - 10.1016/j.bbrc.2015.02.102
M3 - Article
C2 - 25727021
AN - SCOPUS:84925532785
SN - 0006-291X
VL - 459
SP - 288
EP - 293
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -