HIV-1 tat protein induces a migratory phenotype in human fetal microglia by a CCL2 (MCP-1)-dependent echanism: Possible role in NeuroAIDS

Eliseo Eugenin, Gawain Dyer, Tina M. Calderon, Joan W. Berman

Research output: Contribution to journalArticle

67 Scopus citations

Abstract

Acquired immune deficiency syndrome (AIDS) encephalitis and dementia are characterized by neuronal loss, astrogliosis, and microglia activation and migration that contribute to the formation of multinucleated giant cells. Despite extensive evidence of pathological changes in the brain of infected individuals, the mechanisms of human immune deficiency virus type 1 (HIV-1) entry, microglia migration, and viral propagation within the brain are still not completely understood. In this study, we report that the induction of a migratory phenotype in human fetal microglia by the HIV-1 transactivator protein, tat, is mediated by the chemokine, CCL2. CCL2 or tat treatment alone induced rearrangement of actin and the formation of microglial processes. The time course of cell membrane ruffling induced by CCL2 was faster (5-30 min) than that elicited by tat treatment (2-3 h). Our previous data in human fetal microglia showed that tat induces CCL2 expression. Thus, we examined whether tat-induced microglia membrane ruffling and process formation, critical components in cell migration, are mediated by the secretion of CCL2 by these cells. To test this hypothesis, we treated microglia with tat protein in the presence of neutralizing CCL2 antibodies. Co-treatment with neutralizing CCL2 antibodies resulted in the loss of tat-induced membrane ruffling. Tat treatment of microglia induced polarization of CCR2, the receptor for CCL2, to the leading edge of processes, further suggesting a CCL2-dependent mechanism of tat-induced microglia migration. Our data indicate that tat facilitates microglia migration by inducing autocrine CCL2 release. Our results suggest that tat induced CCL2 secretion may be one of the early signals during NeuroAIDS.

Original languageEnglish (US)
Pages (from-to)501-510
Number of pages10
JournalGLIA
Volume49
Issue number4
DOIs
StatePublished - Mar 1 2005
Externally publishedYes

    Fingerprint

Keywords

  • AIDS
  • CCR2
  • Chemokine
  • Dementia

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

Cite this