Novel pathway of human immunodeficiency virus type 1 uptake and release in astrocytes

Jennifer N. Clarke, Julie Anne Lake, Christopher J. Burrell, Steven L. Wesselingh, Paul R. Gorry, Peng Li

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Astrocytes persistently infected with HIV-1 can transmit virus to CD4+ cells, suggesting that astrocytes may be a source of viral persistence and dissemination in the brain. In the present study, we investigated the fate of HIV-1 upon infection of astrocytes. HIV-1 was observed in vesicle-like structures. Unspliced genomic RNA and extrachromosomal HIV-1 DNA were detected in astrocytes, with levels declining over time. The extrachromosomal viral DNA was not de novo reverse transcribed in astrocytes but most likely the products of intravirion reverse transcription present in the virus inoculum. Integrated HIV-1 DNA was not detected in assays sensitive to detect 2 integrated copies of provirus. However, the majority of astrocyte cultures released infectious virus that could be transmitted to CD4+ cells. Our findings suggest a novel pathway of HIV-1 uptake and release in astrocytes that does not necessarily require virus replication, which may contribute to persistence and spread of HIV-1 in the brain.

Original languageEnglish
Pages (from-to)141-155
Number of pages15
JournalVirology
Volume348
Issue number1
DOIs
Publication statusPublished - 25 Apr 2006

Keywords

  • Astrocyte
  • HIV-1
  • Latency
  • Persistence
  • Replication
  • Reservoir

ASJC Scopus subject areas

  • Virology

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