Intrahepatic gene expression during chronic hepatitis C virus infection in chimpanzees
Intrahepatic gene expression during chronic hepatitis C virus infection in chimpanzees
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DOI：
10.1128/jvi.78.24.13779-13792.2004
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发表时间：
2004-12-01
影响因子：
5.4
通讯作者：
Lanford, RE
中科院分区：
文献类型：
--
作者：
Bigger, CB;Guerra, B;Lanford, RE
丙型肝炎病毒（HCV）感染是一个全球性的健康问题，是导致包括肝硬化和肝细胞癌在内的终末期肝病的主要因素。需要更好地了解与疾病进展有关的参数，以开发更好的治疗方法和疾病表现的诊断标记。为了更好地了解持续病毒感染导致宿主基因表达的动态，对10只持续感染HCV的黑猩猩的肝脏进行了DNA微阵列分析。与未感染的对照组相比，慢性感染的动物总共有162个基因受到不同的调控。许多基因在10只慢性感染动物的表达变化中表现出显著的一致性。第二种分析方法确定了971个基因在慢性感染期间表达改变，置信度为99%。与急性解决HCV感染一样，许多干扰素（IFN）刺激基因（ISG）转录升高，表明对IFN和/或双链RNA的持续反应在下游ISG表达中被扩增。因此，HCV的持续感染导致复杂且部分可预测的基因表达模式，尽管调节不同途径的潜在机制尚未明确。单个基因3型感染动物可用于分析，与基因1型感染的表达水平相比，该动物的ISG表达水平降低，许多可能与脂肪变性有关的基因表达增加。基因表达数据与丙型肝炎病毒感染的其他观察结果相一致，允许对丙型肝炎病毒感染的特定方面的调节进行推测。
Hepatitis C virus (HCV) infections represent a global health problem and are a major contributor to end-stage liver disease including cirrhosis and hepatocellular carcinoma. An improved understanding of the parameters involved in disease progression is needed to develop better therapies and diagnostic markers of disease manifestation. To better understand the dynamics of host gene expression resulting from persistent virus infection, DNA microarray analyses were conducted on livers from 10 chimpanzees persistently infected with HCV. A total of 162 genes were differentially regulated in chronically infected animals compared to uninfected controls. Many genes exhibited a remarkable consistency in changes in expression in the 10 chronically infected animals. A second method of analysis identified 971 genes altered in expression during chronic infection at a 99% confidence level. As with acute-resolving HCV infections, many interferon (IFN)stimulated genes (ISGs) were transcriptionally elevated, suggesting an ongoing response to IFN and/or double-stranded RNA which is amplified in downstream ISG expression. Thus, persistent infection with HCV results in a complex and partially predictable pattern of gene expression, although the underlying mechanisms regulating the different pathways are not well defined. A single genotype 3-infected animal was available for analysis, and this animal exhibited reduced levels of ISG expression compared to levels of expression with genotype 1 infections and increased expression of a number of genes potentially involved in steatosis. Gene expression data in concert with other observations from HCV infections permit speculation on the regulation of specific aspects of HCV infection.