Tracking the naturally occurring mutations across the full-length genome of hepatitis B virus of genotype D in different phases of chronic e-antigen-negative infection

Authors

  • S. Ghosh,

    1. Centre for Liver Research, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research, Kolkata, India
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  • R. K. Mondal,

    1. Centre for Liver Research, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research, Kolkata, India
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  • P. Banerjee,

    1. Centre for Liver Research, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research, Kolkata, India
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  • M. Nandi,

    1. Centre for Liver Research, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research, Kolkata, India
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  • S. Sarkar,

    Corresponding author
    • Corresponding author: S. Datta, Centre for Liver Research, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research, 244 A. J. C. Bose Road, Kolkata-700020, India
      E-mail: seemdatt@gmail.com

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  • K. Das,

    1. Centre for Liver Research, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research, Kolkata, India
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  • A. Santra,

    1. Centre for Liver Research, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research, Kolkata, India
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  • S. Banerjee,

    1. Centre for Liver Research, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research, Kolkata, India
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  • A. Chowdhury,

    1. Centre for Liver Research, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research, Kolkata, India
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  • S. Datta

    1. Centre for Liver Research, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research, Kolkata, India
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  • Present address: National Institute of Biomedical Genomics, Kalyani, West Bengal, India.

Abstract

Clin Microbiol Infect 2012; 18: E412–E418

Abstract

Hepatitis B e-antigen (HBeAg)-negative chronic HBV infection is highly prevalent in several parts of the world, including India, with the clinical spectrum ranging from inactive carrier (IC) state to chronic ‘e-negative’ hepatitis B (CHB) and culminating in advanced liver disease such as cirrhosis (LC). The present study has for the first time investigated the natural diversity of HBV belonging to genotype D in treatment-naïve Indian patients representing the above phases of HBeAg-negative infection to identify candidate mutations associated with each disease state. Studies of full-length HBV/D sequences revealed that the progressive accumulation and persistence of mutations in basal core promoter, negative regulatory element, Pre-core region, the B- and T-cell epitopes of X protein as well as deletions in the PreS region contribute significantly to disease progression from IC through CHB to LC. In addition, the development of CHB was associated with a significant increase in viral variants characterized by mutations in enhancer II, preS1 promoter, T-cell epitope of core and B-cell epitope region of PreS1. While few of the mutations were previously reported in the context of HBV genotypes B and C, others had not been documented before. Our results thus highlight a distinct pattern of mutation in HBV/D that may help in predicting clinical outcomes of HBeAg-negative infection and have implications for better clinical management of the patients.

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