Molecular characterization of a new variant of hepatitis b virus in a persistently infected homosexual man

Authors

  • Ramesh A. Bhat,

    1. Department of Laboratory Medicine, University of California, San Francisco, California 94143-0100
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  • Paul P. Ulrich,

    1. Department of Laboratory Medicine, University of California, San Francisco, California 94143-0100
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  • Girish N. Vyas

    Corresponding author
    1. Department of Laboratory Medicine, University of California, San Francisco, California 94143-0100
    • Department of Laboratory Medicine, University of California, San Francisco, CA 94143-0134
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Abstract

Based on the diversity of nucleotide sequences of cloned hepatitis B virus DNA genomes, we have predicted possible replication of genetic variants of human hepatitis B virus. This prediction is exemplified by studies of a chronic carrier of HBsAg/adw2, who lacked anti-HBc but carried exceedingly high levels of hepatitis B virus DNA in serum. Molecular characterization of a number of clones revealed a restriction map that deviated significantly from the typical pattern of the adw2 subtype, especially around the EcoRI site commonly used as a reference point. Mutations appearing consistently in the precore and core regions included (a) mutation in the precore region resulting in a termination codon after the initiation codon, (b) mutation of the core initiation codon and (c) an inframe insert of 36 nucleotides in the precore region with a new initiation site for the core protein.

The 36-nucleotide insertion resulted in a new core protein with 12 extra amino acids at its amino-terminal end. A few scattered point mutations were clustered in the amino-terminal half of the core gene. Although the core protein of this hepatitis B virus variant carried immunologically detectable HBcAg, the absence of a humoral immune response to HBcAg could have been caused by previous infection with human immunodeficiency virus. This naturally occurring human hepatitis B virus variant replicated efficiently without expressing the precore region, confirming previous observations made of the artificial mutants of duck hepatitis B virus.

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