小鼠模型中基础核心启动子/前核心突变对慢性乙型肝炎主要

StephenW

J Med Virol

. 2020 May 19.
doi: 10.1002/jmv.26025. Online ahead of print.
Precise Analysis of the Effect of Basal Core Promoter/Precore Mutations on the Main Phenotype of Chronic Hepatitis B in Mouse Models
Yang Liu  1 , Zhong Hua Zhao  2 , Xiao Qin Lv  1 , Yu Wei Tang  2 , Min Cao  3 , Qin Xiang  1 , Yue Wu  4 , Hua Tang Zhang  2 , Guo Qi Lai  1
Affiliations
Affiliations

    1
    Chongqing Medical University Laboratory Animal Center, Chongqing, China.
    2
    Chongqing Academy of Science and Technology, Chongqing, China.
    3
    Children's Hospital of Chongqing Medical University, Chongqing, China.
    4
    The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

    PMID: 32427358 DOI: 10.1002/jmv.26025

Abstract

High replication and mutation rates of hepatitis B virus (HBV) often lead to reduced or suppressed hepatitis B e antigen expression. The most common mutations are genomic variations in the basal core promoter (BCP) and pre-core (PC) regions. However, the effect of BCP/PC mutations on HBV phenotype in vivo remains unclear. We compared and analyzed BCP/PC mutations and BCP/PC reverse mutations in mouse models. In addition to terminating the expression of HBeAg, BCP/PC mutations also resulted in a significant decrease in HBsAg, HBV DNA, and cccDNA in the early stage, and an obvious increase in serum alanine aminotransferase throughout the transfection period. In both groups, serum HBV DNA was positively correlated with intracellular HBV DNA and cccDNA. Further, we found that IL-4 and L-10 levels were significantly lower in the BCP/PC(M) group than in the BCP/PC(R) group at 4 weeks post injection. However, IL-1β was significantly lower in the BCP/PC(M) group than in the BCP/PC(R) group at 26 weeks post injection. In summary, we precisely analyzed the effect of BCP/PC mutations on the phenotype in vivo, which is important to evaluating disease progression and treatment responses of variable chronic hepatitis B patients. This article is protected by copyright. All rights reserved.

Keywords: Basal core promoter; cccsDNA; chronic hepatitis B; phenotype; pre-core mutations.

This article is protected by copyright. All rights reserved.

StephenW

病毒杂志

。 2020年5月19日。
doi：10.1002 / jmv.26025。在线印刷。
小鼠模型中基础核心启动子/前核心突变对慢性乙型肝炎主要表型的影响的精确分析
杨柳1，中华赵2，吕小琴1，于卫堂2，闵草3，秦翔1，月屋4，花堂张2，郭启来1
隶属关系
隶属关系

    1个
    重庆医科大学实验动物中心，重庆，中国。
    2
    重庆科技学院，中国重庆。
    3
    重庆医科大学附属儿童医院，重庆。
    4
    重庆医科大学附属第二医院，重庆，中国。

    PMID：32427358 DOI：10.1002 / jmv.26025

抽象

乙型肝炎病毒（HBV）的高复制率和突变率通常会导致乙型肝炎e抗原表达降低或抑制。最常见的突变是基础核心启动子（BCP）和前核心（PC）地区的基因组变异。然而，尚不清楚BCP / PC突变对体内HBV表型的影响。我们比较并分析了小鼠模型中的BCP / PC突变和BCP / PC反向突变。除了终止HBeAg的表达外，BCP / PC突变还导致HBsAg，HBV DNA和cccDNA在早期显着降低，并且在整个转染期间血清丙氨酸转氨酶明显增加。在两组中，血清HBV DNA与细胞内HBV DNA和cccDNA正相关。此外，我们发现注射后4周，BCP / PC（M）组的IL-4和L-10水平明显低于BCP / PC（R）组。但是，注射后26周，BCP / PC（M）组的IL-1β明显低于BCP / PC（R）组。总之，我们精确地分析了BCP / PC突变对体内表型的影响，这对于评估可变性慢性乙型肝炎患者的疾病进展和治疗反应非常重要。本文受版权保护。版权所有。

关键词：基础核心启动子cccsDNA;慢性乙型肝炎表型前核心突变。

本文受版权保护。版权所有。