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Inhibition of hepatitis delta virus genomic ribozyme self-cleavage by aminoglycosides

  • Original Paper
  • Published:
Journal of Biomedical Science

Abstract

Subgenomic regions of hepatitis delta virus (HDV) RNA contains ribozyme whose activities are important to viral life cycles and depend on a unique pseudoknot structure. To explore the characters of HDV ribozyme, antibiotics of the aminoglycoside, which has been shown inhibiting self-splicing of group I intron and useful in elucidating its structure, were tested for their effect on HDV genomic ribozyme. Aminoglycosides, including tobramycin, netromycin, neomycin and gentamicin effectively inhibited HDV genomic ribozyme self-cleavage in vitro at a concentration comparable to that inhibiting group I intron self-splicing. The extent of inhibition depended upon the concentration of magnesium ion. Chemical modification mapping of HDV ribozyme RNA indicated that the susceptibility of nucleotide 703 to the modifying agent was enhanced in the presence of tobramycin, suggesting a conformational shift of HDV ribozyme, probably due to an interaction with the aminoglycoside. Finally, we examined the effect of aminoglycoside on HDV cleavage and replication in cell lines, however, none of the aminoglycoside effective in vitro exerted suppressive effects in vivo. Our results represented as an initial effort in utilizing aminoglycoside to probe the structure of HDV ribozyme and to compare its reaction mechanism with those of other related ribozymes.

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Authors and Affiliations

  1. Graduate Institute of Microbiology, National Taiwan University, Taiwan

    Ju-Shin Chia & Hsei-Wei Wang

  2. Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taiwan

    Pei-Jer Chen MD, PhD

  3. Hepatitis Research Center and Graduate Institute of Clinical Medicine, National Taiwan University Hospital, 7 Chung Shan South Road, Taipei, Taiwan (ROC)

    Hui-Lin Wu, Ding-Shinn Chen & Pei-Jer Chen MD, PhD

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  1. Ju-Shin Chia
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  2. Hui-Lin Wu
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  5. Pei-Jer Chen MD, PhD
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Chia, JS., Wu, HL., Wang, HW. et al. Inhibition of hepatitis delta virus genomic ribozyme self-cleavage by aminoglycosides. J Biomed Sci 4, 208–216 (1997). https://doi.org/10.1007/BF02253420

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  • DOI: https://doi.org/10.1007/BF02253420

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