JCI table of contents: April 22, 2008(s thought to cause this problem by disru...)

Date:4/22/2008

s thought to cause this problem by disrupting the function of cells that are the precursors of all blood cells; these cells are known as hematopoietic progenitor cells. Exactly how HIV affects hematopoietic progenitor cells has not been determined, although it seems to be an indirect effect as the cells are not themselves infected with HIV. New data, generated by Stphane Prost and colleagues, at the Institute of Emerging Disease and Innovative Therapies, CEA, France, have now indicated that the HIV protein Nef disrupts the function of hematopoietic progenitor cells.

In the study, production of the protein Nef was shown to be essential for the monkey form of HIV (SIV) to disrupt hematopoietic progenitor cell function in vivo and ex vivo. The ability of both SIV and HIV Nef to cause this problem was dependent on the hematopoietic progenitor cells expressing the protein PPAR-gamma. Further, when PPAR-gamma agonists were administered to macaques they impaired hematopoietic progenitor cell function. Disruption of hematopoietic progenitor cell function by both PPAR-gamma agonists and SIV and HIV Nef was associated with downregulation of the signaling molecules STAT5A and STAT5B, indicating that Nef is likely to impair blood cell development by targeting a PPAR-gamma/STAT5 signaling pathway. The authors have therefore suggested that PPAR-gamma antagonists might be of benefit to both individuals infected with HIV and those with blood celldeficiency disorders. As noted by the authors and, in an accompany commentary, Frank Kirchhoff and Guido Silvestri, these data also have implications for PPAR-gamma agonists, which are currently used to treat individuals with type 2 diabetes.

TITLE: Human and simian immunodeficiency viruses deregulate early hematopoiesis through a Nef/PPAR-gamma/STAT5 signaling pathway in macaques

AUTHOR CONTACT:
Stphane Prost
Institute of Emerging Disease and Innovative Therapies, CEA, Fontenay-aux-Roses, France.
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Contact: Karen Honey press_releases@the-jci.org 215-573-1850 Journal of Clinical Investigation Source:Eurekalert

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