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 Zhanqing Zhang Xinxin Zhang Lungen Lu Hai Li Mengji Lu Jiming Zhang
The Journal of Infectious Diseases, Volume 217, Issue 7, 13 March 2018, Pages 1044–1054, https://doi.org/10.1093/infdis/jix683
Published:
02 January 2018
Abstract
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