差异表达的肝内基因有助于在无活性的载体阶段控制乙型肝

StephenW

Differentially expressed intrahepatic genes contribute to control of hepatitis B virus replication in the inactive carrier phase
Hongyan Liu Fahong Li Xiaoyong Zhang Jie Yu Jinyu Wang Jia Jia Xueping Yu Zhongliang Shen Zhenghong Yuan Xiaonan Zhang ... Show more
The Journal of Infectious Diseases, jix683, https://doi.org/10.1093/infdis/jix683
Published:
02 January 2018

Abstract
Background

The natural history of chronic HBV infection was divided into four phases. Patients in the inactive carrier status (IC) and immune tolerant (IT) phase had normal ALT 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 siRNAs 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 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.

StephenW

差异表达的肝内基因有助于在无活性的载体阶段控制乙型肝炎病毒的复制
Hongyan Liu Fahong李晓勇张杰于金玉王佳贾雪萍于忠良沉正宏袁晓楠张...显示更多
“传染病杂志”，jix683，https://doi.org/10.1093/infdis/jix683
发布时间：
2018年1月2日

抽象
背景

慢性HBV感染的自然史分为四个阶段。处于非活动载体状态（IC）和免疫耐受（IT）阶段的患者具有正常的ALT水平，但是巨大的不同病毒载量。 IC阶段低病毒复制状态的机制尚不清楚。
方法

我们通过对肝脏活组织检查的微阵列分析确定了83例慢性乙型肝炎患者的肝内转录组，并使用特定的siRNA在体外筛选差异调节基因对HBV复制的影响。
结果

区分活动性慢性肝炎与IT和IC的基因谱主要由免疫相关基因组成。 IT和IC阶段之间的肝脏转录组基本相似，并且109个表达基因显着不同。通过系统筛选，鉴定出5个候选基因，包括在IC阶段比在IT阶段表达更高的EVA1A，以在细胞模型中调节HBV复制和基因表达。
结论

在慢性活动性肝炎阶段，免疫相关通路上调，而在IT和IC阶段则不上调。在IC阶段高表达的一些肝内基因可能参与HBV复制的控制，并确定HBV感染的失活状态。