Low-level HIV replication in mixed glial cultures is associated with alterations in the processing of p55Gag

Andrew V. Albright, Robin M. Vos, Francisco González-Scarano

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

We report a novel long-lived infection model in human mixed glial cultures (microglia) whereby cells harbor replication-competent HIV-1 for up to 2.5 months after infection; a model that potentially mimics latency within the central nervous system (CNS). Infection of mixed glial cultures in the presence of serum, cytokines, and growth factors (activating conditions) resulted in a robust productive infection of microglial cells as previously described for purified microglia. In contrast, similar mixed glial cells cultured in serum-free medium without cytokines or growth factors (mirroring a nonactivated CNS) supported HIV-1 entry, reverse transcription, integration, and transcription, yet released little or no infectious virus. We found instead that nonactivated mixed glial cells expressed almost 10-fold less Gag protein, but more importantly, analysis of the intracellular Gag products in quiescent cells showed an aberrant p55/p24 Gag processing phenotype that appeared to be due to the premature activity of the viral protease. These results suggest that the cellular environment in nonactivated microglia cells in these mixed glial cultures is not conducive to proper Gag processing and virus release. This long-lived infection model will be useful in identifying factors that are key for viral maturation in cells of the macrophage lineage.

Original languageEnglish (US)
Pages (from-to)328-339
Number of pages12
JournalVirology
Volume325
Issue number2
DOIs
StatePublished - Aug 1 2004

Keywords

  • Glial cultures
  • HIV replication
  • Microglia
  • p55

ASJC Scopus subject areas

  • Virology

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