Varied assembly and RNA editing efficiencies between genotypes I and II hepatitis D virus and their implications

Authors

  • Sheng-Chieh Hsu,

    1. Institutes of Microbiology and Immunology, National Yang-Ming University School of Medicine, Taipei, Taiwan, Republic of China
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  • Wan-Jr Syu,

    1. Institutes of Microbiology and Immunology, National Yang-Ming University School of Medicine, Taipei, Taiwan, Republic of China
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  • I-Jane Sheen,

    1. Division of Gastroenterology, Department of Medicine, Veterans General Hospital, Taipei, Taiwan, Republic of China
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  • Hui-Ting Liu,

    1. Institutes of Microbiology and Immunology, National Yang-Ming University School of Medicine, Taipei, Taiwan, Republic of China
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  • King-Song Jeng,

    1. Division of Molecular and Genomic Medicine Research, National Health Research Institutes, Taipei, Taiwan, Republic of China
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  • Jaw-Ching Wu

    Corresponding author
    1. Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan, Republic of China
    2. Division of Gastroenterology, Department of Medicine, Veterans General Hospital, Taipei, Taiwan, Republic of China
    • Institute of Clinical Medicine, Division of Gastroenterology, Department of Medicine, Veterans General Hospital, Taipei 112, Taiwan. fax: (886) 2-28749437.
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Abstract

The mechanisms that link genotypes of hepatitis D virus (HDV) with clinical outcomes have not yet been elucidated. Genotypic variations are unevenly distributed along the sequences of hepatitis delta antigens (HDAgs). Of these variations, the packaging signal at the C-terminus has a divergence of 74% between genotypes I and II. In this report, we address the issue of whether these high variations between genotypes affect assembly efficiency of HDV particles and editing efficiency of RNA. Viral package systems of transfection with expression plasmids of hepatitis B surface antigen and HDAgs or whole genomes of HDV consistently indicate that the package efficiency of genotype I HDV is higher than that of genotype II. Segment swapping of large-form HDAg indicates that the C-terminal 19-residue region plays a key role for the varied assembly efficiencies. Also, the editing efficiency of genotype I HDV is higher than that of genotype II. The nucleotide and structural changes surrounding the editing site may explain why genotype II HDV has a low RNA editing efficiency. The findings of in vitro assembly systems were further supported by the observations that patients infected with genotype II had significantly lower alanine transaminase (ALT) levels, more favorable outcomes (P < .05), and a trend to have lower serum HDV RNA levels as compared with those infected with genotype I HDV (P = .094). In conclusion, genotype II HDV secretes fewer viral particles than genotype I HDV does, which in turn may reduce the extent of infection of hepatocytes and result in less severe hepatic inflammation.

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