Transcriptional Control of HIV Replication by Multiple Modulators and Their Implication for a Novel Antiviral Therapy

Abstract

Transcriptional regulation is critical for the human immunodeficiency virus 1 (HIV-1) life cycle and is the only step at which the virus amplifies the content of its genetic information. Numerous known and still unknown transcriptional factors, both host and viral, regulate HIV-1 gene expression and latency. This article is a comprehensive review of transcription factors involved in HIV-1 gene expression and presents the significant implications of nuclear factor kappa B (NF-κB) and the HIV-1 transactivator of transcription (Tat) protein. We include recent findings on chromatin remodeling toward HIV transcription and its therapeutic implication is also discussed. The current status of small-molecular-weight compounds that affect HIV transcription is also described.

Low SAMHD1 expression following T-cell activation and proliferation renders CD4+ T cells susceptible to HIV-1

“…It might also be of interest to understand the molecular determinants modulating SAMHD1 expression. In particular, as some transcriptional factors are important for HIV-1 replication [36,37], the study of their relation with SAMHD1 expression may be of importance.…”

Post-transcriptional gene silencing, transcriptional gene silencing and human immunodeficiency virus

“…Provirus refers to the viral form that has been integrated into the cell's genome and is inherited through each cell division. Latent means it is transcriptionally inactive, but is able to re-activate after stimulation [16][17][18][19] and is capable of causing substantial viremia when therapy ceases [20,21] . The viral reservoir, a term used to refer to the latently infected cells as a whole, is maintained throughout the life span of an infected individual.…”

Interaction between Endogenous Bacterial Flora and Latent HIV Infection

“…Maintenance of HIV latency is a multifactorial event involving several factors, including (i) the chromatin environment at the site of integration, (ii) transcriptional interference, (iii) a lack of host transcription factors needed for viral gene expression, (iv) the presence of host transcriptional repressors, and (v) epigenetic silencing of viral transcription (32)(33)(34)(35)(36). The elucidation of molecular mechanisms by which HIV type 1 (HIV-1) persists within infected cells provides a basis for a new therapeutic approach aimed toward combining HIV gene expression therapy and an ARV regimen.…”

“…This is carried out by producing an environment permissive for transcription by altering the degree of acetylation and methylation of histones and nonhistone molecules. HDACi compounds such as trichostatin A, trapoxin, valproic acid, sodium butyrate, or vorinostat (VOR; also known as suberoylanilide hydroxamic acid [SAHA]) have the ability to disrupt latent HIV infection in both cell culture models and ex vivo assays using cells from HIV-1-infected patients or latently infected cell lines (36,(79)(80)(81)(82)(83)(84)(85). Archin et al (83) demonstrated that a single dose of VOR increased biomarkers of cellular acetylation and simultaneously increased HIV RNA expression in resting CD4 ϩ cells from HIV-1-infected patients.…”