Epigenetic crosstalk in chronic infection with HIV-1

Abstract

Human immunodeficiency virus 1 (HIV-1) replicates through the integration of its viral DNA into the genome of human immune target cells. Chronically infected individuals thus carry a genomic burden of virus-derived sequences that persists through antiretroviral therapy. This burden consists of a small fraction of intact, but transcriptionally silenced, i.e. latent, viral genomes and a dominant fraction of defective sequences. Remarkably, all viral-derived sequences are subject to interaction with host cellular physiology at various levels. In this review, we focus on epigenetic aspects of this interaction. We provide a comprehensive overview of how epigenetic mechanisms contribute to establishment and maintenance of HIV-1 gene repression during latency. We furthermore summarize findings indicating that HIV-1 infection leads to changes in the epigenome of target and bystander immune cells. Finally, we discuss how an improved understanding of epigenetic features and mechanisms involved in HIV-1 infection could be exploited for clinical use.