Zaitseva M, Lee S, Lapham C, Taffs R, King L, Romantseva T, Manischewitz J, Golding H
Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
Blood. 2000 Nov 1;96(9):3109-17.
The effect of interferon gamma (IFN-gamma) and interleukin 6 (IL-6) on infection of macrophages with human immunodeficiency virus type 1 (HIV-1) was investigated. By using a polymerase chain reaction-based viral entry assay and viral infectivity assay, it was demonstrated that IL-6 and IFN-gamma augmented susceptibility of monocyte-derived macrophages (MDMs) to infection with T-cell tropic CXCR4-utilizing (X4) HIV-1 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-tropic 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-induced Ca(++) flux in MDMs. In contrast to the effect of IFN-gamma on the infection 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 envelopes that correlated with a modest reduction in surface CCR5 and CD4 on MDMs. It was further demonstrated that macrophage inflammatory protein (MIP)-1alpha and MIP-beta secreted by cytokine-treated MDMs augmented their fusion with T-tropic-expressing cells and inhibited their fusion with M-tropic envelope-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.
研究了γ干扰素（IFN-γ）和白细胞介素6（IL-6）对1型人类免疫缺陷病毒（HIV-1）感染巨噬细胞的影响。通过基于聚合酶链反应的病毒进入试验和病毒感染性试验，证明IL-6和IFN-γ增强了单核细胞衍生巨噬细胞（MDM）对利用T细胞趋化性CXCR4的（X4）HIV-1毒株感染的易感性。与这一发现一致，IFN-γ和IL-6增强了MDM与表达T趋化性包膜的细胞的融合。CXCR4配体SDF-1和T22肽可抑制细胞因子处理的MDM与T趋化性包膜增强的融合。IFN-γ和IL-6不影响MDM表面CXCR4的表达或SDF-1诱导的Ca（++）内流。与IFN-γ对MDM感染X4毒株的影响相反，IFN-γ抑制MDM对巨噬细胞趋化性（M趋化性）HIV-1的病毒进入和有效感染。与这一发现一致，IFN-γ诱导与M趋化性包膜的融合减少，这与MDM表面CCR5和CD4的适度减少相关。进一步证明，细胞因子处理的MDM分泌的巨噬细胞炎性蛋白（MIP）-1α和MIP-β增强了它们与表达T趋化性的细胞的融合，并抑制了它们与表达M趋化性包膜的细胞的融合。这些数据表明，在机会性感染或性传播疾病期间产生的促炎细胞因子可能使巨噬细胞易感染X4毒株，进而加速疾病进展。
