title: HIV-Induced Epigenetic Alterations in Host Cells.
abstract: Human immunodeficiency virus (HIV), a member of the Retroviridae family, is a positive-sense, enveloped RNA virus. HIV, the causative agent of acquired immunodeficiency syndrome (AIDS) has two major types, HIV-1 and HIV-2 In HIV-infected cells the single stranded viral RNA genome is reverse transcribed and the double-stranded viral DNA integrates into the cellular DNA, forming a provirus. The proviral HIV genome is controlled by the host epigenetic regulatory machinery. Cellular epigenetic regulators control HIV latency and reactivation by affecting the chromatin state in the vicinity of the viral promoter located to the 5' long terminal repeat (LTR) sequence. In turn, distinct HIV proteins affect the epigenotype and gene expression pattern of the host cells. HIV-1 infection of CD4(+) T cells in vitro upregulated DNMT activity and induced hypermethylation of distinct cellular promoters. In contrast, in the colon mucosa and peripheral blood mononuclear cells from HIV-infected patients demethylation of the FOXP3 promoter was observed, possibly due to the downregulation of DNA methyltransferase 1. For a curative therapy of HIV infected individuals and AIDS patients, a combination of antiretroviral drugs with epigenetic modifying compounds have been suggested for the reactivation of latent HIV-1 genomes. These epigenetic drugs include histone deacetylase inhibitors (HDACI), histone methyltransferase inhibitors (HMTI), histone demethylase inhibitors, and DNA methyltransferase inhibitors (DNMTI).
authors.affiliation: Division of Digestive Diseases, Department of Internal Medicine, University of Cincinnati Medical Center, 231 Albert B. Sabin Way, Cincinnati, OH, 45267-0595, USA.
authors.forename: Enass A
authors.initials: EA
authors.lastname: Abdel-Hameed
authors.affiliation: Division of Asthma Research, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Ji
authors.affiliation: Division of Digestive Diseases, Department of Internal Medicine, University of Cincinnati Medical Center, 231 Albert B. Sabin Way, Cincinnati, OH, 45267-0595, USA. mohamed.shata@uc.edu.|Saint James School of Medicine, Saint Vincent, Saint Vincent and the Grenadines. mohamed.shata@uc.edu.
authors.forename: Mohamed Tarek
authors.initials: MT
authors.lastname: Shata
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D044127:Epigenesis, Genetic; D015967:Gene Expression Regulation, Viral; D016679:Genome, Viral; D015658:HIV Infections / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology*; D015498:HIV-2 / Q000502:physiology*; D006801:Humans; D017735:Virus Latency / Q000502:physiology*
keywords: HIV latency; Histone deacetylase inhibitors; T cell specific genes; de novo methylation; “Shock and kill” therapy