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Conservative Evolution of Hepatitis B Virus Precore and Core Gene During Immune Tolerant Phase in Intrafamilial Transmission

  • RESEARCH ARTICLE
  • Published:
Virologica Sinica

Abstract

Hepatitis B virus (HBV) is characterized with high mutations, which is attributed to the lack of proof-reading of the viral reverse transcriptase and host immune pressure. In this study, 31 HBV chronic carriers from 14 families were enrolled to investigate the evolution of the same original HBV sources in different hosts. Sequences of pre-C and C (pre-C/C) genes were analyzed in eight pairs of HBV-infected mothers with longitudinal sera (at an interval of 6.0–7.2 years) and their children (5.5–6.7 years old), and in 15 adults (21–78 years old) from six families with known intrafamilial HBV infection. The pre-C/C sequences had almost no change in eight mothers during 6.0–7.2 years and their children who were in immune tolerant phase. The pre-C/C sequences from the 15 adults of six families, mostly in the immune-clearance phase or the low replicative phase, showed various diversified mutations between individuals from each family. Compared to a reference stain (GQ205441) isolated nearby, the pre-C/C in individuals in immune tolerant phase showed 98.56%–99.52% homology at nucleotide level and 99.5%–100% homology at amino acid level. In contrast, multiple mutations were developed in the immune-clearance phase or the low replicative phase, affecting immune epitopes in core gene and G1896 in pre-C gene. The results indicate that the evolution of new HBV variants is not mainly resulted from the spontaneous error rate of viral reverse transcription, but from the host immune pressure.

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Acknowledgements

We thank Ms. Zhenhua Feng (Nanjing Drum Tower Hospital, Nanjing 210008, China) for performing sequencing of HBV pre-C/C gene. This study was supported by the National Natural Science Foundation of China (81672002), the Science and Technology Department of Jiangsu Province (BK20161105), and the Jiangsu Provincial Department of Health (H201537), China.

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Author notes

  1. Yuqian Luo and Le Zhang have contributed equally to this work.

Authors and Affiliations

  1. Department of Laboratory Medicine, Nanjing Drum Tower Hospital and Jiangsu Key Laboratory for Molecular Medicine, Nanjing University Medical School, Nanjing, 210008, China

    Yuqian Luo, Le Zhang & Yi-Hua Zhou

  2. Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, 210008, China

    Yimin Dai & Yali Hu

  3. Department of Biostatistics, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, 210008, China

    Biyun Xu

  4. Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing Medical University, Nanjing, 210008, China

    Yi-Hua Zhou

Authors
  1. Yuqian Luo
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  2. Le Zhang
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  3. Yimin Dai
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  4. Yali Hu
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Contributions

YHZ designed the study and critically revised the manuscript; YL and LZ performed the experiments, analyzed data and wrote the manuscript; YD and YH followed the patients, collected and analyzed the clinical data; BX participated in the design and performed the statistical analysis. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Yi-Hua Zhou.

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Conflict of interest

The authors declare no conflict of interests.

Animal and Human Rights Statement

This study was approved by the institutional review boards of Nanjing Drum Tower Hospital, essentially following the ethical guidelines of the Declaration of Helsinki. Before sample collection, written informed consent was obtained from all the patients or their guardians for which identifying information is included in this article.

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Luo, Y., Zhang, L., Dai, Y. et al. Conservative Evolution of Hepatitis B Virus Precore and Core Gene During Immune Tolerant Phase in Intrafamilial Transmission. Virol. Sin. 35, 388–397 (2020). https://doi.org/10.1007/s12250-020-00194-6

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  • DOI: https://doi.org/10.1007/s12250-020-00194-6

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