Quantitative dynamics of hepatitis B basal core promoter and precore mutants bef

StephenW

Research Article
Quantitative dynamics of hepatitis B basal core promoter and precore mutants before and after HBeAg seroconversion

• Hui Nie1, †,
• Alison A. Evans2, 3, †,
• W. Thomas London4,
• Timothy M. Block1, 3, 5,
• Xiangdong David Ren1, 5, 6, ,
  

• 1 Department of Microbiology and Immunology, Drexel University College of Medicine, Doylestown, PA, USA
• 2 School of Public Health, Drexel University, Philadelphia, PA, USA
• 3 Hepatitis B Foundation, Doylestown, PA, USA
• 4 Fox Chase Cancer Center, Philadelphia, PA, USA
• 5 Institute for Hepatitis and Virus Research, Doylestown, PA, USA
• 6 Reniguard Life Sciences Inc., Doylestown, PA, USA
  

• Received 16 August 2011. Revised 16 November 2011. Accepted 23 November 2011. Available online 13 December 2011.
  

• http://dx.doi.org/10.1016/j.jhep.2011.11.012, How to Cite or Link Using DOI
  

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Background & Aims

Hepatitis B e antigen (HBeAg) seroconversion is an important clinical and virological “landmark” during chronic hepatitis B virus (HBV) infection. Mutant viruses carrying the precore G1896A and/or the basal core promoter (BCP) A1762T/G1764A mutations are associated with HBeAg seroconversion. However, the exact role of these mutants in HBeAg seroconversion remains unclear, partly because the evolution of these mutant viruses before and after seroconversion has not been well studied.

Methods

Using our novel mutant quantification methods, the percentage of the mutant viruses was analyzed both cross-sectionally and longitudinally, before and after seroconversion.

Results

Cross-sectional analysis showed that the percentage of both precore and BCP mutants gradually increased with age in the HBeAg-positive population. Follow-up of 18 HBeAg-positive patients revealed that the mutant percentage may stay low and stable for many years, followed by a steady increase in the percentage of G1896A and/or A1762T/G1764A mutants, from <10% to 50–100%, within about 3 years prior to seroconversion. In all cases, increase of mutant percentage was preceded or accompanied by elevated serum alanine aminotransferase. After the seroconversion, the mutant percentage could remain high or decrease significantly, sometimes to below 20%.

Conclusions

Levels of G1896A and A1762T/G1764A mutants (of genotypes B and C) in the HBeAg-positive patients may predict the time of HBeAg seroconversion. The dominance of these mutants in the HBeAg-positive phase is more likely the result of immune selection rather than the enhanced replication capability of the mutants. However, anti-HBe antibody may not be a major selection force for these mutants.

StephenW

研究文章
HBeAg血清转换前后乙型肝炎基本核心启动子和前C区突变的定量动态

    回族Nie1，†
    艾莉森答Evans2，3，†
    W.托马斯London4，
    霍震霆研究BLOCK1，3，5，
    向东大卫REN1，5，6，通讯作者的联系信息，电子邮件通讯作者

    1部微生物学和免疫，德雷克塞尔大学医学院，Doylestown的宾夕法尼亚，美国
    2，美国宾夕法尼亚州费城德雷克塞尔大学公共卫生学院，
    3 B型肝炎基金会，Doylestown的PA，USA
    4福克斯蔡斯癌症中心，美国宾夕法尼亚州费城，
    5肝炎病毒研究，Doylestown的，PA，美国研究所
    6 Reniguard生命科学公司，Doylestown的宾夕法尼亚，美国

    2011年8月16收到。 2011年11月16修。 2011年11月23日接受。 2011年12月13日。

    http://dx.doi.org/10.1016/j.jhep.2011.11.012，如何来引用或链接使用作者

   
背景与目的

B型肝炎e抗原（HBeAg）血清转换是一个重要的临床和病毒学慢性乙型肝炎病毒（HBV）感染过程中的“里程碑”。突变病毒携带前C区G1896A和/或基本核心启动子（BCP）A1762T/G1764A突变与HBeAg血清转换。然而，这些突变在HBeAg血清转换的确切作用尚不清楚，前后转阴这些突变病毒的演变，一方面是因为一直没有得到很好的研究。
方法

突变病毒的比例使用我们的新的突变的定量分析方法，分析了跨分段和纵向，前后转阴。
结果

横断面分析表明，前C区和BCP区突变率在HBeAg阳性的人口年龄逐渐增加。后续18日透露，HBeAg阳性患者突变的比例可能保持低而稳定，多年来在G1896A和/或A1762T/G1764A突变的百分比<10％，稳步上升到50-100％在3年左右前向转阴。在所有情况下，突变率增加之前，或伴有血清谷丙转氨酶升高。的血清转换后，突变的比例可能维持高位或显着降低，有时低于20％。
结论

G1896A和A1762T/G1764A突变在HBeAg阳性患者（基因型B和C）的水平可以预测HBeAg血清转换的时间。这些突变在HBeAg阳性阶段的优势是更有可能的，而不是复制能力增强的突变体的免疫选择的结果。然而，抗-HBe抗体可能无法对这些突变体的主要选择力量。
缩略语

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