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Despite extensive evidence of pathological changes in the brain of infected individuals, the mechanisms of human immune deficiency virus type 1 (HIV\u20101) 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\u20101 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\u201330 min) than that elicited by tat treatment (2\u20133 h). Our previous data in human fetal microglia showed that tat induces CCL2 expression. Thus, we examined whether tat\u2010induced 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\u2010treatment with neutralizing CCL2 antibodies resulted in the loss of tat\u2010induced membrane ruffling. Tat treatment of microglia induced polarization of CCR2, the receptor for CCL2, to the leading edge of processes, further suggesting a CCL2\u2010dependent mechanism of tat\u2010induced 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. \u00a9 2004 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/glia.20137","type":"journal-article","created":{"date-parts":[[2004,12,1]],"date-time":"2004-12-01T19:48:31Z","timestamp":1101930511000},"page":"501-510","source":"Crossref","is-referenced-by-count":63,"title":["HIV\u20101 tat protein induces a migratory phenotype in human fetal microglia by a CCL2 (MCP\u20101)\u2010dependent mechanism: Possible role in NeuroAIDS"],"prefix":"10.1002","volume":"49","author":[{"given":"Eliseo A.","family":"Eugenin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gawain","family":"Dyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina M.","family":"Calderon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan 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