Hepatitis B virus variants with core gene deletions in the evolution of chronic hepatitis B infection.
Hepatitis B virus variants with core gene deletions in the evolution of chronic hepatitis B infection.
复制标题
慢性乙型肝炎感染演变过程中具有核心基因缺失的乙型肝炎病毒变种。
作者：
G. Marinos;F. Torre;S. Günther;Mark George Thomas;H. Will;R. Williams;N. Naoumov
背景与目标
在慢性活动性B型肝炎患者中发现了核心基因缺失的B型肝炎病毒（HBV）基因组变异，但这些变异在慢性HBV感染过程中的意义尚不清楚。本研究的目的是纵向分析在α干扰素治疗和B e抗原（HBeAg）至抗B e抗原（抗-HBe）血清转换的增强免疫压力下HBV核心基因缺失变异体的变化。
方法
对67例HBeAg阳性慢性HBV携带者的358份血清标本进行HBV前C/C基因扩增，随访2-11年。通过凝胶电泳、克隆和DNA测序分析核心基因缺失。
结果
在长期HBV复制和持续肝脏炎症的患者中检测到核心基因缺失（37-250个碱基对）的HBV突变体，总是与野生型菌株一起。它们与显著较低的病毒血症水平和较高的抗-HBe血清转换率相关。核心基因缺失突变体在血清转换后优先消除，与前核心终止密码子的HBV毒株积累相反。
结论
这些数据表明，具有核心基因缺失的HBV变异体可以抑制HBV复制，在增强的免疫压力下不会持续优先于野生型HBV，并且不会赋予对干扰素α治疗的抗性。
BACKGROUND & AIMS
Genomic variants of the hepatitis B virus (HBV) with core gene deletions have been identified in patients with chronic active hepatitis B, but the significance of these mutations in the course of chronic HBV infection remains unknown. The aim of this study was to longitudinally analyze the changes of HBV core gene deletion variants under the enhanced immune pressure of interferon alfa treatment and hepatitis B e antigen (HBeAg) to antibody to hepatitis B e antigen (anti-HBe) seroconversion.
METHODS
HBV precore/core gene was amplified in 358 serum samples from 67 chronic HBV carriers (all HBeAg-positive) followed up for a period of 2-11 years. The core gene deletions were analyzed by gel electrophoresis, cloning, and DNA sequencing.
RESULTS
HBV mutants with core gene deletions (37-250 base pairs) were detected in patients with long-standing HBV replication and ongoing hepatic inflammation, always together with the wild-type strain. They were associated with a significantly lower level of viremia and a high rate of seroconversion to anti-HBe. Core gene deletion mutants were preferentially eliminated after seroconversion, in contrast to the accumulation of HBV strains with a precore stop codon.
CONCLUSIONS
These data indicate that HBV variants with core gene deletions may inhibit HBV replication, do not persist in preference of the wild-type HBV under enhanced immune pressure, and do not confer resistance to interferon alfa treatment.