Differentially Expressed Intrahepatic Genes Contribute to Control of Hepatitis B Virus Replication in the Inactive Carrier Phase
Differentially Expressed Intrahepatic Genes Contribute to Control of Hepatitis B Virus Replication in the Inactive Carrier Phase
复制标题
肝内差异表达基因有助于控制乙型肝炎病毒在非活动携带期的复制
DOI：
10.1093/infdis/jix683
复制
发表时间：
2018-04-01
影响因子：
6.4
通讯作者：
Zhang, Jiming
中科院分区：
文献类型：
--
作者：
Liu, Hongyan;Li, Fahong;Zhang, Jiming
背景
将慢性B型肝炎病毒（HBV）感染的自然史分为4个阶段。处于非活动性携带者（IC）状态和免疫耐受（IT）阶段的患者丙氨酸氨基转移酶水平正常，但病毒载量差异巨大。IC期低病毒复制状态的机制尚不清楚。
方法
我们通过基因芯片技术检测了83例慢性B型肝炎患者肝组织的转录组，并利用特异性小干扰RNA（siRNA）筛选了差异表达基因对HBV复制的影响。
结果
区分慢性活动性肝炎与IT和IC的基因谱主要由免疫相关基因组成。IT和IC期之间的肝脏转录组基本相似，109个表达基因存在显著差异。通过系统筛选，在细胞模型中筛选出EVA1A等5个调控HBV复制和基因表达的候选基因，这些基因在IC期的表达水平高于IT期。
结论
免疫相关通路在慢性肝炎活动期上调，但在IT期和IC期未上调。IC期肝内大量高表达的基因可能参与HBV复制的调控，决定HBV感染的非活动状态。
Background
The natural history of chronic hepatitis B virus (HBV) infection was divided into 4 phases. Patients in the inactive carrier (IC) status and immune tolerant (IT) phase had normal alanine aminotransferase levels but huge different viral loads. The mechanism underlying low viral replication status in IC phase is unknown.
Methods
We determined the intrahepatic transcriptomes of 83 chronic hepatitis B patients by microarray analysis of liver biopsies, and screened the effect of differentially regulated genes on HBV replication using specific small interfering RNAs in vitro.
Results
The gene profile distinguishing active chronic hepatitis from IT and IC was predominantly composed of immune-related genes. The liver transcriptomes between the IT and IC phase were largely similar, and 109 expressed genes were significantly different. By performing systematic screening, 5 candidate genes including EVA1A, which were expressed at a relative higher level in IC phase than IT, were identified to regulate HBV replication and gene expression in cellular models.
Conclusions
The immune-related pathways were up-regulated in the active chronic hepatitis phase but not in the IT and IC phase. A number of intrahepatic genes highly expressed in the IC phase may participate in the control of HBV replication and determine the inactive status of HBV infection.