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

Sheng Chieh Hsu, Wan Jr Syu, I. Jane Sheen, Hui Ting Liu, King Song Jeng, Jaw Ching Wu

Research output: Contribution to journalJournal Article peer-review

58 Scopus citations

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.

Original languageEnglish
Pages (from-to)665-672
Number of pages8
JournalHepatology
Volume35
Issue number3
DOIs
StatePublished - 2002
Externally publishedYes

Fingerprint

Dive into the research topics of 'Varied assembly and RNA editing efficiencies between genotypes I and II hepatitis D virus and their implications'. Together they form a unique fingerprint.

Cite this