2016
DOI: 10.1038/srep31924
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HIV-1 Vpr reactivates latent HIV-1 provirus by inducing depletion of class I HDACs on chromatin

Abstract: HIV-1 Vpr is an accessory protein that induces proteasomal degradation of multiple proteins. We recently showed that Vpr targets class I HDACs on chromatin for proteasomal degradation. Here we show that Vpr induces degradation of HDAC1 and HDAC3 in HIV-1 latently infected J-Lat cells. Degradation of HDAC1 and HDAC3 was also observed on the HIV-1 LTR and as a result, markers of active transcription were recruited to the viral promoter and induced viral activation. Knockdown of HDAC1 and HDAC3 activated the late… Show more

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Cited by 35 publications
(25 citation statements)
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“…It is also reported that inhibition of HDAC3 could induce cell autophagy in human glioma cells [ 29 ], and apoptosis in cholangiocarcinoma [ 30 ]. Besides their utilization as targets in cancer therapy, class I HDACs have gained considerable attention as targets in the search for treatments for degenerative neurological diseases, such as Alzheimer’s and Huntington’s disease [ 20 , 31 , 32 , 33 , 34 ], chronic inflammatory diseases, like asthma and COPD [ 35 , 36 , 37 , 38 ], viral infections [ 39 ], especially for human immunodeficiency virus (HIV) [ 40 , 41 , 42 ], and diabetes [ 22 , 43 , 44 , 45 ]. HDAC3, in particular, is an interesting target in Alzheimer’s disease [ 31 , 46 ], since it is reported that HDAC3 plays an important role in maintaining long-term memory for object location [ 47 ].…”
Section: Resultsmentioning
confidence: 99%
“…It is also reported that inhibition of HDAC3 could induce cell autophagy in human glioma cells [ 29 ], and apoptosis in cholangiocarcinoma [ 30 ]. Besides their utilization as targets in cancer therapy, class I HDACs have gained considerable attention as targets in the search for treatments for degenerative neurological diseases, such as Alzheimer’s and Huntington’s disease [ 20 , 31 , 32 , 33 , 34 ], chronic inflammatory diseases, like asthma and COPD [ 35 , 36 , 37 , 38 ], viral infections [ 39 ], especially for human immunodeficiency virus (HIV) [ 40 , 41 , 42 ], and diabetes [ 22 , 43 , 44 , 45 ]. HDAC3, in particular, is an interesting target in Alzheimer’s disease [ 31 , 46 ], since it is reported that HDAC3 plays an important role in maintaining long-term memory for object location [ 47 ].…”
Section: Resultsmentioning
confidence: 99%
“…In mouse models exposed to vpr via transgenic expression, direct injections, or ALZET osmotic pumps, Balasubramanyam et al and Agarwal et al further demonstrated that vpr impairs adipocyte growth and function, increases adipose inflammation, dysregulates systemic lipid metabolism, and promotes fatty liver disease [28, 33, 34]. Importantly for HIV-infected quiescent CD4 T cells in different tissue reservoirs, circulating vpr can also reactivate latent provirus [89, 90]. Adipocytes exposed to tat and nef in vitro also result in suppression of PPARγ function and adipogenesis, as well as the upregulation of inflammatory cytokines and impairment of glucose uptake [29, 31, 32].…”
Section: Composition and Functions Of Immune Cells In Adipose Tissue mentioning
confidence: 99%
“…Vpr plays an important role in the pathogenesis of SIV in macaques (reviewed in [168]). It induces viral reactivation by promoting the degradation of histone deacetylase 1 and 3 and inducing the production of IL-6 [169, 170]. It promotes activation of HIV promoter by inducing the expression of hypoxia-inducible factor 1-α through increased production of ROS [171, 172].…”
Section: Role Of Hiv-1 Proteins In Neurotoxicitymentioning
confidence: 99%