Genomic analysis of the host response to hepatitis C virus infection
Genomic analysis of the host response to hepatitis C virus infection
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DOI：
10.1073/pnas.202608199
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发表时间：
2002-11-26
影响因子：
11.1
通讯作者：
Chisari, FV
中科院分区：
文献类型：
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作者：
Su, AI;Pezacki, JP;Chisari, FV
我们研究了丙型肝炎病毒（HCV）感染的进展，通过对急性感染的黑猩猩的肝活检进行基因表达分析，这些黑猩猩出现了持续感染、短暂病毒清除或持续清除。观察到常见的反应和结果特异性的表达变化。所有黑猩猩的基因表达模式都与ifn - α反应一致，这种反应与感染的程度和持续时间有关。短暂和持续的病毒清除与ifn - γ诱导的基因和其他参与抗原加工和递呈以及适应性免疫反应的基因的诱导独特相关。在感染的早期阶段，参与脂质代谢的宿主基因也受到差异调节。我们还表明，影响这些生物合成途径的药物可以调节HCV复制子系统中的HCV复制。我们的研究结果揭示了反映感染建立、传播和控制的全基因组转录变化，并揭示了与HCV感染清除相关的潜在独特抗病毒程序。
We have examined the progression of hepatitis C virus (HCV) infections by gene expression analysis of liver biopsies in acutely infected chimpanzees that developed persistent infection, transient viral clearance, or sustained clearance. Both common responses and outcome-specific changes in expression were observed. All chimpanzees showed gene expression patterns consistent with an IFN-alpha response that correlated with the magnitude and duration of infection. Transient and sustained viral clearance were uniquely associated with induction of IFN-gamma-induced genes and other genes involved in antigen processing and presentation and the adaptive immune response. During the early stages of infection, host genes involved in lipid metabolism were also differentially regulated. We also show that drugs that affect these biosynthetic pathways can regulate HCV replication in HCV replicon systems. Our results reveal genome-wide transcriptional changes that reflect the establishment, spread, and control of infection, and they reveal potentially unique antiviral programs associated with clearance of HCV infection.