title: 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 latent HIV-1 provirus and complementation with HDAC3 inhibited Vpr-induced HIV-1 reactivation. Viral reactivation and degradation of HDAC1 and HDAC3 was conserved among Vpr proteins of HV-1 group M. Serum Vpr isolated from patients or the release of virion-incorporated Vpr from viral lysates also activated HIV-1 in latently infected cell lines and PBMCs from HIV-1 infected patients. Our results indicate that Vpr counteracts HIV-1 latency by inducing proteasomal degradation of HDAC1 and 3 leading to reactivation of the viral promoter.
authors.affiliation: Cellular and Molecular Research Center (CMRC), Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences (AJUMS), Ahvaz, 61357-15794, Iran.|Department of Biology, Faculty of Science, University of Isfahan, Isfahan, 81746-73441, Iran.
authors.forename: Bizhan
authors.initials: B
authors.lastname: Romani
authors.affiliation: Department of Human Viral Vaccines, Razi Vaccine and Serum Research Institute, Karaj, 31976-19751, Iran.
authors.forename: Razieh
authors.initials: R
authors.lastname: Kamali Jamil
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.
authors.forename: Pooneh
authors.initials: P
authors.lastname: Rahimi
authors.affiliation: Pilot Biotechnology Department, Pasteur Institute of Iran, Tehran, 13169-43551, Iran.
authors.forename: Seyed Bahman
authors.initials: SB
authors.lastname: Momen
authors.affiliation: Hepatitis and AIDS Department, Pasteur Institute of Iran, Tehran, 13169-43551, Iran.
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.
authors.forename: Elham
authors.initials: E
authors.lastname: Allahbakhshi
mesh_terms: D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D057809:HEK293 Cells; D015658:HIV Infections / Q000378:metabolism* / Q000821:virology; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D056284:Histone Deacetylase 1 / Q000378:metabolism*; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D011401:Promoter Regions, Genetic; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D059748:Proteolysis; D011533:Proviruses / Q000235:genetics / Q000502:physiology*; D014775:Virus Activation; D017735:Virus Latency; D054325:vpr Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*; D000099186:Histone Deacetylase 3
chemical_list: D002843:Chromatin; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases; D046988:Proteasome Endopeptidase Complex; D054325:vpr Gene Products, Human Immunodeficiency Virus; D000099186:Histone Deacetylase 3; C514912:vpr protein, Human immunodeficiency virus 1; C110550:HDAC1 protein, human