Interferon gamma and interleukin 6 modulate the susceptibility of macrophages to human immunodeficiency virus type 1 infection

The effect of interferon gamma (IFN-gamma) and interleukin 6 (IL-6) on infe ction of macrophages with human immunodeficiency virus type 1 (HIV-1) was i nvestigated. By using a polymerase chain reaction-based viral entry assay a nd viral infectivity assay, it was demonstrated that IL-6 and IFN-gamma aug mented susceptibility of monocyte-derived macrophages (MDMs) to infection w ith T-cell tropic CXCR4-utilizing (X4) HIV-I strains. Consistent with this finding, IFN-gamma and IL-6 augmented fusion of MDMs with T-tropic envelope -expressing cells. The enhanced fusion of cytokine-treated MDMs with T-trop ic envelopes was inhibited by the CXCR4 ligand, SDF-1, and by T22 peptide. IFN-gamma and IL-6 did not affect expression of surface CXCR4 or SDF-1-indu ced Ca++ flux in MDMs, In contrast to the effect of IFN-gamma on the infect ion of MDMs with X4 strains, IFN-gamma inhibited viral entry and productive infection of MDMs with macrophage-tropic (M-tropic) HIV-1, Consistent with this finding, IFN-gamma induced a decrease in fusion with M-tropic envelop es that correlated with a modest reduction in surface CCR5 and CD4 on MDMs, It was further demonstrated that macrophage inflammatory protein (MIP)-1 a lpha and MIP-beta secreted by cytokine-treated MDMs augmented their fusion with T-tropic-expressing cells and inhibited their fusion with M-tropic env elope-expressing cells. These data indicate that proinflammatory cytokines, which are produced during opportunistic infections or sexually transmitted diseases, may predispose macrophages to infection with X4 strains that, in turn, could accelerate disease progression. (C) 2000 by The American Socie ty of Hematology.