Prostaglandin E(2) inhibits replication of HIV-1 in macrophages through activation of protein kinase A

Cell Immunol. 2002 Jan;215(1):61-71. doi: 10.1016/s0008-8749(02)00017-5.


Since macrophages are a source of increased PGE(2) in AIDS, we investigated the role of PGE(2) in the replication of HIV-1 in these cells. PGE(2) inhibited HIV-1 replication measured by reverse transcriptase in human monocyte-derived macrophage (MDM). Treatment of MDM with the PGE(1) analog misoprostol, the adenylate cyclase activator forskolin, and the cyclic AMP analog dibutyryl-cyclic AMP (db-cAMP) suppressed HIV replication. The protein kinase A (PKA) activator 8-bromo-cyclic AMP also inhibited HIV-1 replication. Similar results were observed with the entry-independent, latently HIV-infected U1 cells. There was a parallel decrease in HIV-1 mRNA levels following PGE(2) treatment. Co-transfection of the HIV-1 promoter LTR.luciferase, with the vector CMV.Calpha, which expresses the PKA catalytic unit increasing PKA activity, reduced HIV-1 promoter activity. Inhibition of PKA activity with the pMT.RAB vector, a mutant regulatory unit of PKA, augmented HIV-1 promoter activity. In summary, PGE(2) inhibits HIV-1 gene expression in MDM through a PKA-dependent mechanism.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / pharmacology
  • 8-Bromo Cyclic Adenosine Monophosphate / pharmacology
  • Adenylyl Cyclase Inhibitors
  • Bucladesine / pharmacology
  • Cells, Cultured
  • Colforsin / pharmacology
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Dinoprostone / biosynthesis
  • Dinoprostone / pharmacology*
  • Enzyme Activation
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation, Viral / drug effects
  • HIV-1 / drug effects*
  • HIV-1 / genetics
  • HIV-1 / metabolism
  • Humans
  • Kinetics
  • Macrophages / enzymology
  • Macrophages / immunology
  • Macrophages / virology*
  • Misoprostol / pharmacology
  • Monocytes / physiology
  • Promoter Regions, Genetic
  • RNA, Viral / biosynthesis
  • Receptors, CCR5 / metabolism
  • Virus Replication / drug effects*


  • Adenylyl Cyclase Inhibitors
  • Enzyme Inhibitors
  • RNA, Viral
  • Receptors, CCR5
  • Misoprostol
  • Colforsin
  • 8-Bromo Cyclic Adenosine Monophosphate
  • Bucladesine
  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
  • Cyclic AMP-Dependent Protein Kinases
  • Dinoprostone