Vpr- and Nef-dependent induction of RANTES/CCl5 in microglial cells

Qiusheng Si, Mee Ohk Kim, Meng Liang Zhao, Nathaniel R. Landau, Harris Goldstein, Sunhee C. Lee

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

Microglia are pivotal in the pathogenesis of AIDS dementia, as they serve as the major target of HIV infection in the CNS. In addition, activation of microglia correlates best with clinical dementia. Although the β-chemokine RANTES/CCL5 is important in modulating HIV infection as well as cellular activation, no information is available regarding how its expression is regulated in microglia by HIV-1. Here we report that RANTES/CCL5 expression is induced in microglia by HIV-1, but that this requires infection by HIV-1. This conclusion was supported by (1) the delayed kinetics coinciding with viral replication; (2) the lack of effect of X4 viruses; (3) inhibition by the reverse transcriptase inhibitor AZT, and (4) the lack of effect of cytokine antagonists or antibodies. Interestingly, RANTES/CCL5 production was dependent on the viral accessory protein Vpr, in addition to Nef, demonstrating a novel role for Vpr in chemokine induction in primary macrophage-type cells. Furthermore, the specific p38 MAP kinase inhibitor SB203580 augmented chemokine expression in microglia, indicating a negative role played by p38. These data suggest unique features of RANTES/CCL5 regulation by HIV-1 in human microglial cells.

Original languageEnglish (US)
Pages (from-to)342-353
Number of pages12
JournalVirology
Volume301
Issue number2
DOIs
StatePublished - Jan 1 2002

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Keywords

  • AIDS
  • Brain
  • Chemokine
  • Dementia
  • HIV-1
  • Human
  • MAP kinase
  • Microglia
  • RANTES

ASJC Scopus subject areas

  • Virology

Cite this

Si, Q., Kim, M. O., Zhao, M. L., Landau, N. R., Goldstein, H., & Lee, S. C. (2002). Vpr- and Nef-dependent induction of RANTES/CCl5 in microglial cells. Virology, 301(2), 342-353. https://doi.org/10.1006/viro.2002.1613