Peroxisome Proliferator-activated Receptor Gamma Agonists Inhibit HIV-1 Replication in Macrophages by Transcriptional and Post-transcriptional Effects

Michael M. Hayes, Brian R. Lane, Steven R. King, David M. Markovitz, and Michael J. Coffey

From the Divisions of Pulmonary and Critical Care Medicine, Rheumatology, and _Infectious Diseases and the Graduate Program in Cellular and Molecular Biology, University of Michigan Medical Center, Ann Arbor, Michigan 48109 Published, JBC Papers in Press, February 14, 2002.

The PPARγ agonist ciglitazone inhibited HIV-1 replication in a dose-dependent manner in acutely infected human MDM. In addition, cyPG and ciglitazone reduced HIV replication in latently infected and viral entry-independent U1 cells, suggesting an effect at the level of HIV gene expression. Ciglitazone also suppressed HIV-1 mRNA levels as measured by reverse transcriptase PCR, in parallel with the decrease in reverse transcriptase activity. Co-transfection of PPARγ wild type vectors and treatment with PPARγ agonists inhibited HIV-1 promoter activity in U937 cells. Activation of PPARγ also decreased HIV-1 mRNA stability following actinomycin D treatment.

In summary, our experimental findings implicate PPARγ as an important factor in the suppression of HIV-1 gene expression in MDM by cyPG. Thus natural and synthetic PPARγ g agonists may play a role in controlling HIV-1 infection in macrophages.