Antiretroviral Therapy Down-Regulates Innate Antiviral Response Genes in Patients With AIDS in Sub-Saharan Africa
Antiretroviral Therapy Down-Regulates Innate Antiviral Response Genes in Patients With AIDS in Sub-Saharan Africa
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DOI：
10.1097/qai.0b013e3181ef4963
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发表时间：
2010-12-01
影响因子：
3.6
通讯作者：
Bohjanen, Paul R.
中科院分区：
文献类型：
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作者：
Boulware, David R.;Meya, David B.;Bohjanen, Paul R.
目的：HIV发病机制的特点是病毒介导的免疫损伤、抗病毒免疫反应和免疫激活之间的破坏性失衡。我们描述了成功的抗逆转录病毒治疗（ART）的效果，以确定hiv相关基因表达的广度和模式。方法：在一项前瞻性观察性纵向队列研究中，我们对10名未接受ART治疗的乌干达艾滋病患者（中位数为30 CD4(+)/mL），使用Affymetrix U133_Plus2.0微阵列在开始ART治疗后的0、2、4、8和24周检测外周血mRNA基因谱。结果：基于线性回归模型，我们鉴定出160个mRNA转录本在24周内ART治疗后的每个点持续下调，48个mRNA转录本上调（调整P < 0.05），在这208个转录本中，大约一半代表迄今未被识别的ART应答基因，三分之一没有已知的功能。已知功能的下调基因编码了先天抗病毒反应的介质，包括抗病毒限制因子、模式识别受体和干扰素反应蛋白，以及免疫激活、细胞增殖和凋亡的介质。结论：通过使用ART阻断病毒刺激，我们发现了先天抗病毒免疫中涉及的转录物，包括抗病毒限制因子和模式识别受体，这些转录物以前并不知道是由HIV感染诱导的。
Objective: HIV pathogenesis is characterized by destructive imbalances between virus-mediated immune damage, antiviral immune responses, and immune activation. We characterized the effects of successful antiretroviral therapy (ART) to identify the breadth and patterns of HIV-associated gene expression.Methods: In a prospective observational, longitudinal cohort study of 10 ART-naive Ugandans with AIDS (median 30 CD4(+)/mL), we measured mRNA gene profiles in peripheral blood using Affymetrix U133_Plus2.0 microarrays at 0, 2, 4, 8, and 24 weeks after ART initiation.Results: We identified 160 mRNA transcripts that were consistently down-regulated and 48 that were up-regulated after ART at each point over 24 weeks based on linear regression modeling (adjusted P < 0.05), Of these 208 transcripts, approximately half represent heretofore unrecognized ART-responsive genes and one-third have no known function. The down-regulated genes with known function encoded mediators of innate antiviral responses, including antiviral restriction factors, pattern recognition receptors, and interferon response proteins, and mediators of immune activation, cellular proliferation, and apoptosis.Conclusions: By using ART to block the viral stimulus, we identified transcripts involved in innate antiviral immunity, including antiviral restriction factors and pattern recognition receptors, that were not previously known to be induced by HIV infection.