title: Transcriptional control of HIV latency: cellular signaling pathways, epigenetics, happenstance and the hope for a cure.
abstract: Replication-competent latent HIV-1 proviruses that persist in the genomes of a very small subset of resting memory T cells in infected individuals under life-long antiretroviral therapy present a major barrier towards viral eradication. Multiple molecular mechanisms are required to repress the viral trans-activating factor Tat and disrupt the regulatory Tat feedback circuit leading to the establishment of the latent viral reservoir. In particular, latency is due to a combination of transcriptional silencing of proviruses via host epigenetic mechanisms and restrictions on the expression of P-TEFb, an essential co-factor for Tat. Induction of latent proviruses in the presence of antiretroviral therapy is expected to enable clearance of latently infected cells by viral cytopathic effects and host antiviral immune responses. An in-depth comprehensive understanding of the molecular control of HIV-1 transcription should inform the development of optimal combinatorial reactivation strategies that are intended to purge the latent viral reservoir.
authors.affiliation: Department of Molecular Biology and Microbiology, Case Western Reserve University, School of Medicine, Cleveland, OH 44106, United States.
authors.forename: Uri
authors.initials: U
authors.lastname: Mbonye
authors.affiliation: Department of Molecular Biology and Microbiology, Case Western Reserve University, School of Medicine, Cleveland, OH 44106, United States. Electronic address: jxk153@cwru.edu.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Karn
mesh_terms: D044127:Epigenesis, Genetic; D015967:Gene Expression Regulation, Viral; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D014158:Transcription, Genetic; D017735:Virus Latency; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000378:metabolism
chemical_list: D054322:tat Gene Products, Human Immunodeficiency Virus
keywords: 7SK snRNP; BRD4; Epigenetics; HIV latency; Inducible proviruses; Latency reversal; NF-κB; P-TEFb; Tat