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

40 Citations (Scopus)

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 - 2002

Fingerprint

Chemokine CCL5
Microglia
HIV-1
Chemokines
HIV Infections
Dementia
Viral Regulatory and Accessory Proteins
Reverse Transcriptase Inhibitors
p38 Mitogen-Activated Protein Kinases
Acquired Immunodeficiency Syndrome
Macrophages
Cytokines
Viruses
Antibodies
Infection

Keywords

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

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

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

Vpr- and Nef-dependent induction of RANTES/CCl5 in microglial cells. / Si, Qiusheng; Kim, Mee Ohk; Zhao, Meng Liang; Landau, Nathaniel R.; Goldstein, Harris; Lee, Sunhee C.

In: Virology, Vol. 301, No. 2, 2002, p. 342-353.

Research output: Contribution to journalArticle

Si, Q, Kim, MO, Zhao, ML, Landau, NR, Goldstein, H & Lee, SC 2002, 'Vpr- and Nef-dependent induction of RANTES/CCl5 in microglial cells', Virology, vol. 301, no. 2, pp. 342-353. https://doi.org/10.1006/viro.2002.1613
Si, Qiusheng ; Kim, Mee Ohk ; Zhao, Meng Liang ; Landau, Nathaniel R. ; Goldstein, Harris ; Lee, Sunhee C. / Vpr- and Nef-dependent induction of RANTES/CCl5 in microglial cells. In: Virology. 2002 ; Vol. 301, No. 2. pp. 342-353.
@article{d537a8142ebb44b99b4fa3bda4432e9f,
title = "Vpr- and Nef-dependent induction of RANTES/CCl5 in microglial cells",
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.",
keywords = "AIDS, Brain, Chemokine, Dementia, HIV-1, Human, MAP kinase, Microglia, RANTES",
author = "Qiusheng Si and Kim, {Mee Ohk} and Zhao, {Meng Liang} and Landau, {Nathaniel R.} and Harris Goldstein and Lee, {Sunhee C.}",
year = "2002",
doi = "10.1006/viro.2002.1613",
language = "English (US)",
volume = "301",
pages = "342--353",
journal = "Virology",
issn = "0042-6822",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Vpr- and Nef-dependent induction of RANTES/CCl5 in microglial cells

AU - Si, Qiusheng

AU - Kim, Mee Ohk

AU - Zhao, Meng Liang

AU - Landau, Nathaniel R.

AU - Goldstein, Harris

AU - Lee, Sunhee C.

PY - 2002

Y1 - 2002

N2 - 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.

AB - 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.

KW - AIDS

KW - Brain

KW - Chemokine

KW - Dementia

KW - HIV-1

KW - Human

KW - MAP kinase

KW - Microglia

KW - RANTES

UR - http://www.scopus.com/inward/record.url?scp=0036401929&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036401929&partnerID=8YFLogxK

U2 - 10.1006/viro.2002.1613

DO - 10.1006/viro.2002.1613

M3 - Article

VL - 301

SP - 342

EP - 353

JO - Virology

JF - Virology

SN - 0042-6822

IS - 2

ER -