title: A Natural Product from Polygonum cuspidatum Sieb. Et Zucc. Promotes Tat-Dependent HIV Latency Reversal through Triggering P-TEFb's Release from 7SK snRNP.
abstract: The latent reservoirs of HIV represent a major impediment to eradication of HIV/AIDS. To overcome this problem, agents that can activate latent HIV proviruses have been actively sought after, as they can potentially be used in combination with the highly active antiretroviral therapy (HAART) to eliminate the latent reservoirs. Although several chemical compounds have been shown to activate latency, they are of limited use due to high toxicity and poor clinical outcomes. In an attempt to identify natural products as effective latency activators from traditional Chinese medicinal herbs that have long been widely used in human population, we have isolated procyanidin C-13,3',3"-tri-O-gallate (named as REJ-C1G3) from Polygonum cuspidatum Sieb. et Zucc., that can activate HIV in latently infected Jurkat T cells. REJ-C1G3 preferentially stimulates HIV transcription in a process that depends on the viral encoded Tat protein and acts synergistically with prostratin (an activator of the NF-κB pathway) or JQ1 (an inhibitor of Brd4) to activate HIV latency. Our mechanistic analyses further show that REJ-C1G3 accomplishes these tasks by inducing the release of P-TEFb, a host cofactor essential for Tat-activation of HIV transcription, from the cellular P-TEFb reservoir 7SK snRNP.
authors.affiliation: School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, China.
authors.forename: Shuiyuan
authors.initials: S
authors.lastname: Yang
authors.affiliation: School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, China.|Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, United States of America.
authors.forename: Huasong
authors.initials: H
authors.lastname: Lu
authors.affiliation: School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, China.
authors.forename: Hongchao
authors.initials: H
authors.lastname: You
authors.affiliation: School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, China.
authors.forename: Man
authors.initials: M
authors.lastname: Ni
authors.affiliation: School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Shan
authors.affiliation: School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Lin
authors.affiliation: School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.affiliation: School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Chen
authors.affiliation: School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, China.|Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, United States of America.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, China.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Xue
mesh_terms: D001381:Azepines / Q000494:pharmacology; D001688:Biological Products / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004357:Drug Synergism; D045468:Fallopia japonica / Q000737:chemistry*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D010703:Phorbol Esters / Q000494:pharmacology; D042925:Positive Transcriptional Elongation Factor B / Q000378:metabolism*; D044945:Proanthocyanidins / Q000494:pharmacology; D017411:Ribonucleoproteins, Small Nuclear / Q000378:metabolism*; D020079:Terminal Repeat Sequences / Q000235:genetics; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014230:Triazoles / Q000494:pharmacology; D017735:Virus Latency / Q000187:drug effects*; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
chemical_list: C561695:(+)-JQ1 compound; D001381:Azepines; D001688:Biological Products; D010703:Phorbol Esters; D044945:Proanthocyanidins; D017411:Ribonucleoproteins, Small Nuclear; D014230:Triazoles; C485184:enhanced green fluorescent protein; D054322:tat Gene Products, Human Immunodeficiency Virus; D049452:Green Fluorescent Proteins; C070999:prostratin; D042925:Positive Transcriptional Elongation Factor B