HIV type 1 infection of human macrophages induces an upregulation of manganese superoxide dismutase gene that may protect cells from death.
It has been previously demonstrated that HIV-1 infection induces a downregulation of MnSOD transcription in CD4+ lymphocytes. Using clinical isolates of macrophage-tropic HIV-1 strains we report here that conversely, purified normal human monocyte-derived macrophages (MDMs) overexpress the manganese superoxide dismutase (MnSOD) gene in response to infection and viral replication. This upregulation of MnSOD gene expression is concomitant with tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) production and treatment of HIV-1-infected MDMs with a specific transcriptional inhibitor of TNF-alpha synthesis counteracts the HIV-1-induced MnSOD gene activation. Moreover, TNF-alpha but not IL-6 addition mimicks the effects of HIV-1 infection on MnSOD gene regulation in normal MDM cultures. These observations strongly suggest that the MnSOD gene induction detected in HIV-1-infected MDMs is triggered by TNF-alpha produced in culture supernatants in parallel to HIV-1 particle release. In contrast to MnSOD, HIV-1 infection or replication in human MDMs has no effect on copper-zinc superoxide dismutase (Cu/ZnSOD) gene expression.
Raoul
H
H
CEA, Service de Neurovirologie, DSV/DRM/SSA, Institut Paris Sud sur les Cytokines, Fontenay aux Roses, France.
Le Naour
R
R
Blond
D
D
Dormont
D
D
D015152:Blotting, Northern; D016923:Cell Death / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000187:drug effects; D015497:HIV-1 / Q000254:growth & development*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism* / Q000821:virology*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology; D015854:Up-Regulation; D014779:Virus Replication
D016207:Cytokines; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D013482:Superoxide Dismutase