Elevated levels of macrophage migration inhibitory factor (MIF) in the plasma of HIV-1-infected patients and in HIV-1-infected cell cultures: a relevant role on viral replication

Virology. 2010 Mar 30;399(1):31-38. doi: 10.1016/j.virol.2009.12.018. Epub 2010 Jan 20.

Abstract

The cytokine macrophage migration inhibitory factor (MIF) is involved in the pathogenesis of inflammatory and infectious diseases, however its role in HIV-1 infection is unknown. Here we show that HIV-1-infected patients present elevated plasma levels of MIF, that HIV-1-infected peripheral blood mononuclear cells (PBMCs) release a greater amount of MIF, and that the HIV-1 envelope glycoprotein gp120 induces MIF secretion from uninfected PBMCs. The HIV-1 replication in PBMCs declines when these cells are treated with anti-MIF antibodies, and exposure of HIV-1-infected cells to the ABC-transporter inhibitor probenecid results in inhibition of MIF secretion. The addition of recombinant MIF (rhMIF) to HIV-1-infected PBMCs enhances viral replication of CCR5- or CXCR4-tropic HIV-1 isolates. Using a T CD4(+) cell lineage containing an HIV long terminal repeats (LTR)-Luciferase construct, we detected that rhMIF promotes transcription from HIV-1 LTR. Our results show that HIV-1 induces MIF secretion and suggest that MIF influences the HIV-1 biology through activation of HIV-1 LTR.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / antagonists & inhibitors
  • Cell Line
  • HIV Envelope Protein gp120 / physiology
  • HIV Infections / blood
  • HIV Infections / virology*
  • HIV Long Terminal Repeat / physiology
  • HIV-1*
  • Humans
  • Intramolecular Oxidoreductases / biosynthesis
  • Intramolecular Oxidoreductases / blood*
  • Leukocytes, Mononuclear / physiology
  • Macrophage Migration-Inhibitory Factors / biosynthesis
  • Macrophage Migration-Inhibitory Factors / blood*
  • Probenecid / pharmacology
  • Recombinant Proteins
  • Virus Replication / physiology*

Substances

  • ATP-Binding Cassette Transporters
  • HIV Envelope Protein gp120
  • Macrophage Migration-Inhibitory Factors
  • Recombinant Proteins
  • gp120 protein, Human immunodeficiency virus 1
  • Intramolecular Oxidoreductases
  • MIF protein, human
  • Probenecid