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.
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.
Regis
Eduardo G
EG
Laboratory on Thymus Research, Oswaldo Cruz Institute/FIOCRUZ, Rio de Janeiro, RJ, Brazil.
Barreto-de-Souza
Victor
V
Laboratory on Thymus Research, Oswaldo Cruz Institute/FIOCRUZ, Rio de Janeiro, RJ, Brazil.
Morgado
Mariza G
MG
Laboratory of AIDS and Molecular Immunology, Oswaldo Cruz Institute/FIOCRUZ, Rio de Janeiro, RJ, Brazil.
Bozza
Marcelo T
MT
Department of Immunology, Institute of Microbiology, Federal University of Rio de Janeiro, RJ, Brazil.
Leng
Lin
L
Yale School of Medicine, CT, USA.
Bucala
Richard
R
Yale School of Medicine, CT, USA.
Bou-Habib
Dumith C
DC
Laboratory on Thymus Research, Oswaldo Cruz Institute/FIOCRUZ, Rio de Janeiro, RJ, Brazil. Electronic address: dumith@ioc.fiocruz.br.
D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors; D002460:Cell Line; D015699:HIV Envelope Protein gp120 / Q000502:physiology; D015658:HIV Infections / Q000097:blood / Q000821:virology*; D016325:HIV Long Terminal Repeat / Q000502:physiology; D015497:HIV-1; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000096:biosynthesis / Q000097:blood*; D007963:Leukocytes, Mononuclear / Q000502:physiology; D008263:Macrophage Migration-Inhibitory Factors / Q000096:biosynthesis / Q000097:blood*; D011339:Probenecid / Q000494:pharmacology; D011994:Recombinant Proteins; D014779:Virus Replication / Q000502:physiology*
D018528:ATP-Binding Cassette Transporters; D015699:HIV Envelope Protein gp120; D008263:Macrophage Migration-Inhibitory Factors; D011994:Recombinant Proteins; C514793:gp120 protein, Human immunodeficiency virus 1; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human; D011339:Probenecid