Logo image
Deployment of the human immunodeficiency virus type 1 protein arsenal: combating the host to enhance viral transcription and providing targets for therapeutic development
Journal article   Open access   Peer reviewed

Deployment of the human immunodeficiency virus type 1 protein arsenal: combating the host to enhance viral transcription and providing targets for therapeutic development

Satinder Dahiya, Michael R Nonnemacher and Brian Wigdahl
Journal of general virology, v 93(Pt 6), pp 1151-1172
Jun 2012
PMID: 22422068
url
https://doi.org/10.1099/vir.0.041186-0View
Published, Version of Record (VoR) Open

Abstract

Anti-HIV Agents - pharmacology HIV-1 - metabolism Gene Expression Regulation, Viral - drug effects HIV Infections - genetics HIV Infections - virology Humans Viral Proteins - genetics Viral Proteins - antagonists & inhibitors HIV-1 - genetics Viral Proteins - metabolism Animals Virus Replication HIV Infections - drug therapy HIV Infections - metabolism
Despite the success of highly active antiretroviral therapy in combating human immunodeficiency virus type 1 (HIV-1) infection, the virus still persists in viral reservoirs, often in a state of transcriptional silence. This review focuses on the HIV-1 protein and regulatory machinery and how expanding knowledge of the function of individual HIV-1-coded proteins has provided valuable insights into understanding HIV transcriptional regulation in selected susceptible cell types. Historically, Tat has been the most studied primary transactivator protein, but emerging knowledge of HIV-1 transcriptional regulation in cells of the monocyte-macrophage lineage has more recently established that a number of the HIV-1 accessory proteins like Vpr may directly or indirectly regulate the transcriptional process. The viral proteins Nef and matrix play important roles in modulating the cellular activation pathways to facilitate viral replication. These observations highlight the cross talk between the HIV-1 transcriptional machinery and cellular activation pathways. The review also discusses the proposed transcriptional regulation mechanisms that intersect with the pathways regulated by microRNAs and how development of the knowledge of chromatin biology has enhanced our understanding of key protein-protein and protein-DNA interactions that form the HIV-1 transcriptome. Finally, we discuss the potential pharmacological approaches to target viral persistence and enhance effective transcription to purge the virus in cellular reservoirs, especially within the central nervous system, and the novel therapeutics that are currently in various stages of development to achieve a much superior prognosis for the HIV-1-infected population.

Metrics

7 Record Views
7 citations in Scopus

Details

UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

InCites Highlights

Data related to this publication, from InCites Benchmarking & Analytics tool:

Web of Science research areas
Biotechnology & Applied Microbiology
Virology
Logo image