The host response to smallpox: Analysis of the gene expression program in peripheral blood cells in a nonhuman primate model
The host response to smallpox: Analysis of the gene expression program in peripheral blood cells in a nonhuman primate model
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DOI：
10.1073/pnas.0405759101
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发表时间：
2004-10-19
影响因子：
11.1
通讯作者：
Relman, DA
中科院分区：
文献类型：
--
作者：
Rubins, KH;Hensley, LE;Relman, DA
天花在人类历史上发挥了无与伦比的作用，仍然是对公共卫生的重大潜在威胁。尽管这种疾病具有重要的历史意义，但我们对天花病毒的基本病理生理学或致病机制知之甚少。为了更好地了解天花的发病机制和天花与宿主的相互作用，我们研究了食蟹猴出血性天花的分子和细胞特征。我们使用cDNA微阵列分析了来自22只感染动物的连续血液样本中宿主基因的表达模式。天花病毒感染引起外周血中基因表达的显著和时间上的协调模式。特别感兴趣的是似乎代表干扰素反应、细胞增殖、免疫球蛋白基因表达、病毒剂量依赖的基因表达模式以及病毒对宿主免疫反应的调节的特征。面对压倒性的全身性感染，肿瘤坏死因子α/核因子-kappaB激活的转录程序实际上是缺失的，这表明花椒基因产物可能会消除这种反应。这些结果提供了天花感染期间宿主转录反应的详细图像，并可能有助于指导诊断、治疗和预防策略的发展。
Smallpox has played an unparalleled role in human history and remains a significant potential threat to public health. Despite the historical significance of this disease, we know little about the underlying pathophysiology or the virulence mechanisms of the causative agent, variola virus. To improve our understanding of variola pathogenesis and variola-host interactions, we examined the molecular and cellular features of hemorrhagic smallpox in cynomolgus macaques. We used cDNA microarrays to analyze host gene expression patterns in sequential blood samples from each of 22 infected animals. Variola infection elicited striking and temporally coordinated patterns of gene expression in peripheral blood. Of particular interest were features that appear to represent an IFN response, cell proliferation, immunoglobulin gene expression, viral dose-dependent gene expression patterns, and viral modulation of the host immune response. The virtual absence of a tumor necrosis factor alpha/NF-kappaB-activated transcriptional program in the face of an overwhelming systemic infection suggests that variola gene products may ablate this response. These results provide a detailed picture of the host transcriptional response during smallpox infection, and may help guide the development of diagnostic, therapeutic, and prophylactic strategies.