HIV-induced epigenetic alterations in host cells

Abstract

Human immunodefi ciency virus (HIV), a member of the Retroviridae family, is a positive-sense, enveloped RNA virus. HIV, the causative agent of acquired immunodefi ciency 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 demethyla tion 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).