Interferon-alpha drives monocyte gene expression in chronic unsuppressed HIV-1 infection.
Interferon-alpha drives monocyte gene expression in chronic unsuppressed HIV-1 infection.
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DOI：
10.1097/qad.0b013e32833ac623
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发表时间：
2010-06-19
期刊：
影响因子：
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通讯作者：
Pulliam L
中科院分区：
文献类型：
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作者：
Rempel H;Sun B;Calosing C;Pillai SK;Pulliam L
目的：HIV-1感染使先天免疫系统失调并改变白细胞基因表达。目的有两个方面：确定HIV-1感染对外周血单核细胞基因表达的影响，并确定导致基因表达改变的主要因素。设计和方法：在一项横断面研究中（n= 55），从11名HIV-1血清阴性对照，22名HIV-1血清阳性低病毒载量（LVL）个体和22名HIV-1血清阳性高病毒载量（HVL）个体中分离出CD14+单核细胞。使用高密度芯片收集对照组、LVL和HVL个体的单核细胞基因表达数据。我们评估了三种HIV-1疾病相关的外周因子，干扰素(IFN)-α， IFN-γ和脂多糖（LPS）作为引起单核细胞失调的候选因子，通过比较研究个体和体外用这些因子处理的单核细胞之间的基因表达谱。对HIV-1阳性个体的血浆进行LPS和可溶性CD14的定量测定。结果：hiv -1病毒载量高于10,000 RNA拷贝/ml （HVL）的感染者单核细胞表现为活化表型。基因表达的表征揭示了对病毒感染的持续免疫反应，包括炎症和趋化性。体外用IFN-α、IFN-γ或LPS处理的HIV-1血清阴性单核细胞的基因表达分析表明，IFN-α最准确地再现了HIV-1 HVL谱。即使在LPS和sCD14水平最高的HIV-1个体中，也没有检测到LPS诱导的基因表达特征。结论：HIV-1病毒血症个体的单核细胞基因表达主要是由IFN-α引起的，而LVL个体具有非活化表型。在单核细胞中，没有与LPS暴露相关的可识别的表达谱。
Objectives:HIV-1 infection dysregulates the innate immune system and alters leukocyte-gene expression. The objectives were two fold: to characterize the impact of HIV-1 infection on peripheral monocyte gene expression and to identify the predominant factor (s) responsible for altered gene expression.Design and methods:In a cross-sectional study (n= 55), CD14+ monocytes were isolated from 11 HIV-1 seronegative controls, 22 HIV-1 seropositive individuals with low-viral loads (LVL) and 22 HIV-1 seropositive individuals with high-viral loads (HVL). Monocyte gene expression data were collected for control, LVL and HVL individuals using high-density microarrays. We evaluated three HIV-1 disease-related peripheral factors, interferon (IFN)-α, IFN-γ and lipopolysaccharide (LPS) as candidates causing monocyte dysregulation, by comparing gene expression profiles between study individuals and monocytes treated with these factors in vitro. Plasma from HIV-1 positive individuals was quantified for LPS and soluble CD14.Results:Monocytes from HIV-1-infected individuals with viral loads above 10 000 RNA copies/ml (HVL) displayed an activated phenotype. Characterization of gene expression revealed an ongoing immune response to viral infection including inflammation and chemotaxis. Gene expression analysis of in-vitro-treated HIV-1 seronegative monocytes with IFN-α, IFN-γ or LPS demonstrated that IFN-α most accurately recapitulated the HIV-1 HVL profile. No LPS-induced gene expression signature was detected even in HIV-1 individuals with the highest LPS and sCD14 levels.Conclusion:Monocyte gene expression in individuals with HIV-1 viremia is predominantly due to IFN-α, whereas individuals with LVL have a nonactivated phenotype. In monocytes, there was no discernible expression profile linked to LPS exposure.