HIV Type 1 Infection of Human Macrophages Induces an Upregulation of Manganese Superoxide Dismutase Gene That May Protect Cells from Death

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Abstract
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 α (TNF-α) and interleukin 6 (IL-6) production and treatment of HIV-1-infected MDMs with a specific transcriptional inhibitor of TNF-α synthesis counteracts the HIV-1-induced MnSOD gene activation. Moreover, TNF-α 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-α 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.

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