Human Immunodeficiency Virus Type-1 (HIV-1) Transcriptional Regulation, Latency and Therapy in the Central Nervous System.

Joseph Hokello,Priya Tyagi,Alok Bhushan,Mudit Tyagi,Adhikarimayum Lakhikumar Sharma

doi:10.3390/vaccines9111272

Abstract

The central nervous system (CNS) is highly compartmentalized and serves as a specific site of human immunodeficiency virus (HIV) infection. Therefore, an understanding of the cellular populations that are infected by HIV or that harbor latent HIV proviruses is imperative in the attempts to address cure strategies, taking into account that HIV infection and latency in the CNS may differ considerably from those in the periphery. HIV replication in the CNS is reported to persist despite prolonged combination antiretroviral therapy due to the inability of the current antiretroviral drugs to penetrate and cross the blood–brain barrier. Consequently, as a result of sustained HIV replication in the CNS even in the face of combination antiretroviral therapy, there is a high incidence of HIV-associated neurocognitive disorders (HAND). This article, therefore, provides a comprehensive review of HIV transcriptional regulation, latency, and therapy in the CNS.

Highlights

CD4+ T cells, as well as monocytes and macrophages, are the primary cellular targets for productive human immunodeficiency virus (HIV)-1 infection [5,6,7], in the brain, macrophages and microglia are the main cell types productively infected by Human immunodeficiency virus type-1 (HIV-1), and virus production in the central nervous system (CNS) is not seen before the onset of acquired immunodeficiency syndrome (AIDS) [8,9]
Leon-Rivera et al [53] most recently characterized the mechanism of CNS viral reservoir establishment and replenishment using the peripheral blood mononuclear cells (PBMCs) of HIV patients on prolonged combination antiretroviral therapy (cART) and established that monocytes from PBMCs with integrated HIV proviruses that were transcriptionally active selectively transmigrated across the human blood–brain barrier (BBB) model
Whereas HIV transcriptional regulation in peripheral cells is majorly Tat-dependent through Tat interactions with the transcription response (TAR) RNA stem–loop structure, HIV

Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Human immunodeficiency virus type-1 (HIV-1) remains one of the most serious public health challenges [1,2,3,4]. CD4+ T cells, as well as monocytes and macrophages, are the primary cellular targets for productive HIV-1 infection [5,6,7], in the brain, macrophages and microglia are the main cell types productively infected by HIV-1, and virus production in the CNS is not seen before the onset of acquired immunodeficiency syndrome (AIDS) [8,9]. HIV-associated injuries of the CNS are believed to be mediated by numerous soluble factors that are released by microglial cells following. These soluble factors include both viral and cellular factors, some of which can directly induce neuronal injury and damage through interactions with receptors on neuronal membranes.

HIV Transcriptional Regulation in the CNS

HIV Latency in the CNS

Neuro-HIV Drugs and Therapy in the CNS

Conclusions