PMID- 23166597
OWN - NLM
STAT- MEDLINE
DCOM- 20130506
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 11
DP  - 2012
TI  - Selective histonedeacetylase inhibitor M344 intervenes in HIV-1 latency through 
      increasing histone acetylation and activation of NF-kappaB.
PG  - e48832
LID - 10.1371/journal.pone.0048832 [doi]
LID - e48832
AB  - BACKGROUND: Histone deacetylase (HDAC) inhibitors present an exciting new 
      approach to activate HIV production from latently infected cells to potentially 
      enhance elimination of these cells and achieve a cure. M344, a novel HDAC 
      inhibitor, shows robust activity in a variety of cancer cells and relatively low 
      toxicity compared to trichostatin A (TSA). However, little is known about the 
      effects and action mechanism of M344 in inducing HIV expression in latently 
      infected cells. METHODOLOGY/PRINCIPAL FINDINGS: Using the Jurkat T cell model of 
      HIV latency, we demonstrate that M344 effectively reactivates HIV-1 gene 
      expression in latently infected cells. Moreover, M344-mediated activation of the 
      latent HIV LTR can be strongly inhibited by a NF-kappaB inhibitor aspirin. We further 
      show that M344 acts by increasing the acetylation of histone H3 and histone H4 at 
      the nucleosome 1 (nuc-1) site of the HIV-1 long terminal repeat (LTR) and by 
      inducing NF-kappaB p65 nuclear translocation and direct RelA DNA binding at the nuc-1 
      region of the HIV-1 LTR. We also found that M344 synergized with prostratin to 
      activate the HIV-1 LTR promoter in latently infected cells. 
      CONCLUSIONS/SIGNIFICANCE: These results suggest the potential of M344 in 
      anti-latency therapies and an important role for histone modifications and NF-kappaB 
      transcription factors in regulating HIV-1 LTR gene expression.
FAU - Ying, Hao
AU  - Ying H
AD  - State Key Laboratory of Genetic Engineering, Institute of Genetics, School of 
      Life Sciences, Fudan University, Shanghai, China.
FAU - Zhang, Yuhao
AU  - Zhang Y
FAU - Zhou, Xin
AU  - Zhou X
FAU - Qu, Xiying
AU  - Qu X
FAU - Wang, Pengfei
AU  - Wang P
FAU - Liu, Sijie
AU  - Liu S
FAU - Lu, Daru
AU  - Lu D
FAU - Zhu, Huanzhang
AU  - Zhu H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121115
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (DNA Primers)
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - 0 (Histones)
RN  - 0 (Hydroxamic Acids)
RN  - 0 (NF-kappa B)
RN  - 0 (Phorbol Esters)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - 36015-30-2 (Propidium)
RN  - 3X2S926L3Z (trichostatin A)
RN  - 58IFB293JI (Vorinostat)
RN  - 60857-08-1 (prostratin)
SB  - IM
MH  - Acetylation/drug effects
MH  - Active Transport, Cell Nucleus/drug effects
MH  - Blotting, Western
MH  - Chromatin Immunoprecipitation
MH  - DNA Primers/genetics
MH  - Drug Synergism
MH  - Flow Cytometry
MH  - Gene Expression Regulation, Viral/*drug effects
MH  - Green Fluorescent Proteins/metabolism
MH  - HEK293 Cells
MH  - HIV Long Terminal Repeat/drug effects/genetics
MH  - *HIV-1
MH  - Histone Deacetylase Inhibitors/*pharmacology
MH  - Histones/*metabolism
MH  - Humans
MH  - Hydroxamic Acids/*pharmacology
MH  - Immunohistochemistry
MH  - Jurkat Cells
MH  - Microscopy, Fluorescence
MH  - NF-kappa B/*metabolism
MH  - Phorbol Esters/pharmacology
MH  - Propidium
MH  - Virus Latency/*drug effects
MH  - Vorinostat
PMC - PMC3499534
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/11/21 06:00
MHDA- 2013/05/07 06:00
PMCR- 2012/11/15
CRDT- 2012/11/21 06:00
PHST- 2012/03/21 00:00 [received]
PHST- 2012/10/05 00:00 [accepted]
PHST- 2012/11/21 06:00 [entrez]
PHST- 2012/11/21 06:00 [pubmed]
PHST- 2013/05/07 06:00 [medline]
PHST- 2012/11/15 00:00 [pmc-release]
AID - PONE-D-12-08315 [pii]
AID - 10.1371/journal.pone.0048832 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(11):e48832. doi: 10.1371/journal.pone.0048832. Epub 2012 Nov 15.