Astrocyte infection by HIV-1: mechanisms of restricted virus replication, and role in the pathogenesis of HIV-1-associated dementia.

Paul R. Gorry, Chi Ong, Janine Thorpe, Sylvie Bannwarth, Katherine A. Thompson, Anne Gatignol, Steven Wesselingh, Damian F J Purcell

Research output: Chapter in Book/Report/Conference proceedingChapter

142 Citations (Scopus)

Abstract

Astrocytes are the most numerous cell type in the brain, and their physiological roles are essential for normal brain function. Studies of post-mortem brain tissue samples from individuals with AIDS have revealed that a small proportion of astrocytes are infected by HIV-1 which is linked to the development of HIV-associated dementia (HIVD), a frequent clinical manifestation of HIV-1 disease affecting up to 20% of infected adults. However, astrocyte infection by HIV-1 in vivo is generally non-productive, and can only be readily detected by sensitive techniques that detect HIV-1 RNA or proviral DNA. Similarly, primary astrocyte cultures and astrocytic cell lines can be permissive to infection by HIV-1 strains, but are refractory to efficient HIV-1 expression. In efforts to delineate the molecular mechanisms underlying the "restricted" infection, several studies have demonstrated that efficient HIV-1 replication is blocked in astrocytes at different steps of the virus life cycle, including virus entry, reverse transcription, nucleocytoplasmic HIV-1 RNA transport, translation of viral RNA, and maturation of progeny virions. However, the relative importance of each of these possible replication blocks in restricting HIV-1 replication in astrocytes is unclear. Moreover, how restricted astrocyte infection contributes to the development of HIVD is unknown. This review surveys the current in vitro models of restricted HIV-1 replication in astrocytes, and provides an analysis of the available evidence supporting a role for astrocyte infection in the pathogenesis of HIVD. A greater understanding of the fate of HIV-1 in astrocytes may assist in the identification of viral reservoirs in the central nervous system, novel therapies for the treatment of HIVD, and also novel strategies to suppress HIV-1 replication in CD4+ cells of the immune system.
Original languageEnglish
Title of host publicationCurrent HIV research
Pages463-73
Number of pages11
DOIs
Publication statusPublished - 2003

Publication series

NameCurrent HIV research
Volume1

Keywords

  • AIDS Dementia Complex
  • AIDS Dementia Complex: virology
  • Astrocytes
  • Astrocytes: virology
  • Cytokines
  • Gene Products, rev
  • Gene Products, rev: physiology
  • HIV Long Terminal Repeat
  • HIV Long Terminal Repeat: physiology
  • HIV-1
  • HIV-1: physiology
  • Humans
  • Neurotoxins
  • Protein Biosynthesis
  • RNA-Binding Proteins
  • RNA-Binding Proteins: physiology
  • Receptors, HIV
  • Receptors, HIV: physiology
  • Transcription, Genetic
  • Virus Replication
  • eIF-2 Kinase
  • eIF-2 Kinase: metabolism
  • rev Gene Products, Human Immunodeficiency Virus

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