Publications & Reports

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

Gorry PR, Ong C, Thorpe J, Bannwarth S, Thompson KA, Gatignol A, Wesselingh SL, Purcell DF
Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Victoria, Australia. gorry@burnet.edu.au

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.

Publication

  • Journal: Current HIV Research
  • Published: 01/10/2003
  • Volume: 1
  • Issue: 4
  • Pagination: 463-473

Health Issue