HIV TYPE-1 INFECTION OF HUMAN MACROPHAGES INDUCES AN UP-REGULATION OFMANGANESE SUPEROXIDE-DISMUTASE GENE THAT MAY PROTECT CELLS FROM DEATH

It has been previously demonstrated that HIV-1 infection induces a dow nregulation of MnSOD transcription in CD4(+) lymphocytes, Using clinic al isolates of macrophage-tropic HIV-1 strains we report here that con versely, purified normal human monocyte-derived macrophages (MDMs) ove rexpress the manganese superoxide dismutase (MnSOD) gene in response t o infection and viral replication. This upregulation of MnSOD gene exp ression 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 count eracts the HIV-1-induced MnSOD gene activation, Moreover, TNF-alpha bu t not IL-6 addition mimicks the effects of HIV-1 infection on MnSOD ge ne regulation in normal MDM cultures. These observations strongly sugg est that the MnSOD gene induction detected in HIV-1-infected MDMs is t riggered by TNF-alpha produced in culture supernatants in parallel to HIV-1 particle release, In contrast to MnSOD, HIV-1 infection or repli cation in human MDMs has no effect on copper-zinc superoxide dismutase (Cu/ZnSOD) gene expression.