Format

Send to

Choose Destination
J Biol Chem. 2016 Feb 5;291(6):2696-711. doi: 10.1074/jbc.M115.689018. Epub 2015 Dec 17.

HIV-1 Vpr Protein Induces Proteasomal Degradation of Chromatin-associated Class I HDACs to Overcome Latent Infection of Macrophages.

Author information

1
From the Department of Biology, Faculty of Science, University of Isfahan, Isfahan 81746-73441, Iran, Cellular and Molecular Research Center (CMRC), Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences (AJUMS), Ahvaz 61357-15794, Iran, and.
2
From the Department of Biology, Faculty of Science, University of Isfahan, Isfahan 81746-73441, Iran.
3
Hepatitis and AIDS Department, Pasteur Institute of Iran, Tehran 13169-43551, Iran.
4
Hepatitis and AIDS Department, Pasteur Institute of Iran, Tehran 13169-43551, Iran mrasadeghi@pasteur.ac.ir.
5
Cellular and Molecular Research Center (CMRC), Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences (AJUMS), Ahvaz 61357-15794, Iran, and abakhshi_e@ajums.ac.ir.

Abstract

Mechanisms underlying HIV-1 latency remain among the most crucial questions that need to be answered to adopt strategies for purging the latent viral reservoirs. Here we show that HIV-1 accessory protein Vpr induces depletion of class I HDACs, including HDAC1, 2, 3, and 8, to overcome latency in macrophages. We found that Vpr binds and depletes chromatin-associated class I HDACs through a VprBP-dependent mechanism, with HDAC3 as the most affected class I HDAC. De novo expression of Vpr in infected macrophages induced depletion of HDAC1 and 3 on the HIV-1 LTR that was associated with hyperacetylation of histones on the HIV-1 LTR. As a result of hyperacetylation of histones on HIV-1 promotor, the virus established an active promotor and this contributed to the acute infection of macrophages. Collectively, HIV-1 Vpr down-regulates class I HDACs on chromatin to counteract latent infections of macrophages.

KEYWORDS:

E3 ubiquitin ligase; HIV1 Vpr; histone deacetylase (HDAC); human immunodeficiency virus (HIV); infection; latency; macrophage; proteasome

PMID:
26679995
PMCID:
PMC4742738
DOI:
10.1074/jbc.M115.689018
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center