AIDSWEEKLY Plus; Monday, November 28, 2005
Staff Medical Writers

According to a study from the United States, "The hematopoietic compartments act as long-term reservoirs for human immunodeficiency virus type-1 (HIV-1). Although hematopoietic progenitor cells (HPCs) are rarely infectable, HPCs committed to the megakaryocytic lineage can be infected and support a productive infection by both the X4 and R5 strains of HIV-1.

"Indeed, in contrast to the CD34+ progenitors, the lineage-committed HPCs express high levels of the HIV-1 coreceptors, CXCR4 and CCR5. The HIV-1 transactivator (Tat) protein has been shown to alter coreceptor expression in T lymphocytes and macrophages."

"We hypothesized that Tat may regulate co-receptor expression in lineage-specific HPCs as well. We have monitored the effects of Tat protein on coreceptor expression and on lineage-specific differentiation, using the HPC cell line, K562," wrote D. Mondal and coworkers at Louisiana State University.

The investigators reported, "Butyric acid (BA)-induced erythroid differentiation in K562 cells was suppressed by 1100 ng/mL of Tat, as evident from a 70-80% decrease in hemoglobin (Hb) production and a 10-30-fold decrease in glycophorin-A expression. However, Tat treatment enhanced phorbol myristate acetate (PMA)-induced megakaryocytic differentiation, as evident from a 180-210% increase in H-3-serotonin uptake and a 5-12-fold increase in CD61 expression."

"Tat did not significantly alter coreceptor expression in erythroid cells. However," the authors continued, "Tat cotreatment profoundly effected both CXCR4 and CCR5 gene expression and protein levels in megakaryocytic cells. In PMA-stimulated cells, Tat increased CXCR4 and decreased in CCR5 expression, this was potentiated in cells chronically exposed to Tat.

"Tat protein suppresses erythroid and facilitates megakaryocytic differentiation of K562 cells. In megakaryocytic cells, Tat differentially effected CXCR4 and CCR5 expression," they wrote.

The scientists concluded, "Because megakaryocytes may play a crucial role in HIV-1 infectivity in viral reservoirs, our findings implicate a role for Tat protein in dictating coreceptor usage in lineage-committed HPCs."

Mondal and colleagues published the results of their research in Experimental Biology and Medicine (The HIV-1 Tat protein selectively enhances CXCR4 and inhibits CCR5 expression in megakaryocytic K562 cells. Exp Biol Med (Maywood). 2005 Oct;230(9):631-44.

For additional information, contact D. Mondal, Louisiana State University, Health Science Center, Dept. of Pharmacology, School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112, USA.

The publisher of the journal Experimental Biology and Medicine can be contacted at: Society Experimental Biology Medicine, 195 West Spring Valley Avenue, Maywood, NJ 07607-1727, USA.

Keywords: New Orleans, Louisiana, United States, HIV-1 Tat Protein, CCR5, CXCR4, Megakaryocytes, K562 Cells.

This article was prepared by AIDS Weekly editors from staff and other reports.

Reference

Mondal D, Williams CA, Ali M, et al., "The HIV-1 Tat protein selectively enhances CXCR4 and inhibits CCR5 expression in megakaryocytic K562 cells" Exp Biol Med (Maywood). 2005 Oct;230(9):631-44.

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