title: HIV-1 Vpr Protein Induces Proteasomal Degradation of Chromatin-associated Class I HDACs to Overcome Latent Infection of Macrophages.
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.
authors.affiliation: 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.
authors.forename: Bizhan
authors.initials: B
authors.lastname: Romani
authors.affiliation: From the Department of Biology, Faculty of Science, University of Isfahan, Isfahan 81746-73441, Iran.
authors.forename: Nima Shaykh
authors.initials: NS
authors.lastname: Baygloo
authors.affiliation: Hepatitis and AIDS Department, Pasteur Institute of Iran, Tehran 13169-43551, Iran.
authors.forename: Mojtaba
authors.initials: M
authors.lastname: Hamidi-Fard
authors.affiliation: Hepatitis and AIDS Department, Pasteur Institute of Iran, Tehran 13169-43551, Iran mrasadeghi@pasteur.ac.ir.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Aghasadeghi
authors.affiliation: 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.
authors.forename: Elham
authors.initials: E
authors.lastname: Allahbakhshi
mesh_terms: D000107:Acetylation; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D015971:Gene Expression Regulation, Enzymologic; D057809:HEK293 Cells; D015658:HIV Infections / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000502:physiology*; D006367:HeLa Cells; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D059748:Proteolysis; D017735:Virus Latency / Q000502:physiology*; D054325:vpr Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*
chemical_list: D002843:Chromatin; D006657:Histones; D054325:vpr Gene Products, Human Immunodeficiency Virus; C514912:vpr protein, Human immunodeficiency virus 1; D046988:Proteasome Endopeptidase Complex; D006655:Histone Deacetylases
keywords: E3 ubiquitin ligase; HIV1 Vpr; histone deacetylase (HDAC); human immunodeficiency virus (HIV); infection; latency; macrophage; proteasome