前S1启动子区域的取代与乙型肝炎病毒的病毒调节有关

StephenW

A substitution in the pre-S1 promoter region is associated with the viral regulation of hepatitis B virus

    Suguru Ogura†, Masahiko Tameda†, Kazushi SugimotoEmail author, Makoto Ikejiri, Masanobu Usui, Masaaki Ito and Yoshiyuki Takei

†Contributed equally
Virology Journal201916:59

https://doi.org/10.1186/s12985-019-1169-x

©  The Author(s). 2019

    Received: 24 July 2018Accepted: 23 April 2019Published: 2 May 2019

Abstract
Background

Much evidence has demonstrated the influence of Hepatitis B virus (HBV) mutations on the clinical course of HBV infection. As large (L) protein plays a crucial role for viral entry, we hypothesized that mutations in the pre-S1 promoter region might affect the expression of L protein and subsequently change the biological characters of virus.
Methods

Patients infected with genotype C HBV were enrolled for analysis. HBV DNA sequences were inserted into a TA cloning vector and analyzed. To evaluate the effects of mutations in the pre-S1 promoter region, promoter activity and the expression of mRNA and L protein were analyzed using HepG2 cells.
Results

In total, 35 patients were enrolled and 13 patients (37.1%) had a single base substitution in the pre-S1 promoter region; the most frequent substitution was a G-to-A substitution at the 2765th base (G2765A) in the Sp1 region. The HBV viral load showed a negative correlation with the substitution ratio of the Sp1 region or G2765A (r = − 0.493 and − 0.473, respectively). Among those with a viral load ≤5.0 log IU/ml, patients with the G2765A substitution showed a significantly lower HBV viral load than those with the wild-type sequence. HepG2 cells transfected with the G2765A substitution vector showed reduced luciferase activity of the pre-S1 promoter, as well as reduced expression of pre-S1 mRNA and L protein. Furthermore, the G2765A substitution greatly reduced the L protein expression level of vector-produced virus particles.
Conclusion

G2765A substitution in the pre-S1 promoter reduced the expression of L protein and resulted in a low viral load and less severe disease in chronic HBV infections.
Keywords

    Hepatitis B virus
    Mutation
    Pre-S1 promoter
    L protein

StephenW

前S1启动子区域的取代与乙型肝炎病毒的病毒调节有关

    Suguru Ogura†，Masahiko Tameda†，Kazushi Sugimoto电子书作者，Makoto Ikejiri，Masanobu Usui，Masaaki Ito和Yoshiyuki Takei

†同等贡献
Virology Journal201916：59

https://doi.org/10.1186/s12985-019-1169-x

©The Author（s）。 2019

    收稿日期：2018年7月24日接受日期：2019年4月23日出版日期：2019年5月2日

抽象
背景

大量证据表明乙型肝炎病毒（HBV）突变对HBV感染临床过程的影响。由于大（L）蛋白在病毒进入中起着至关重要的作用，我们假设前S1启动子区域的突变可能会影响L蛋白的表达，从而改变病毒的生物学特性。
方法

招募感染基因型C HBV的患者进行分析。将HBV DNA序列插入TA克隆载体中并进行分析。为了评估前S1启动子区域中突变的影响，使用HepG2细胞分析启动子活性和mRNA和L蛋白的表达。
结果

总共招募了35名患者，13名患者（37.1％）在前S1启动子区域进行了单碱基替换;最常见的取代是Sp1区第2765碱基（G2765A）的G-to-A取代。 HBV病毒载量与Sp1区或G2765A的替代率呈负相关（分别为r = -0.493和-0.473）。在病毒载量≤5.0logIU/ ml的患者中，具有G2765A取代的患者显示出比具有野生型序列的患者显着更低的HBV病毒载量。用G2765A取代载体转染的HepG2细胞显示前S1启动子的荧光素酶活性降低，以及前S1 mRNA和L蛋白的表达降低。此外，G2765A取代大大降低了载体产生的病毒颗粒的L蛋白表达水平。
结论

前S1启动子中的G2765A取代降低了L蛋白的表达，并导致低病毒载量和慢性HBV感染中较轻的疾病。
关键词

    乙型肝炎病毒
    突变
    前S1启动子
    L蛋白

StephenW

https://virologyj.biomedcentral. ... 6/s12985-019-1169-x