Logo image
Back
Action of Inhibitors on Accumulation of Processed Hepatitis Delta Virus RNAs
Journal article   Open access   Peer reviewed

Action of Inhibitors on Accumulation of Processed Hepatitis Delta Virus RNAs

Jinhong Chang, Xingcao Nie, Severin Gudima and John Taylor
Journal of virology, v 80(7), pp 3205-3214
01 Apr 2006
DOI: https://doi.org/10.1128/JVI.80.7.3205-3214.2006
PMID: 16537588
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1128/jvi.80.7.3205-3214.2006View
Published, Version of Record (VoR)Open Access (License Unspecified),  Open

Abstract

Genome and Regulation of Viral Gene Expression
Hepatitis delta virus (HDV) replication involves processing and accumulation of three RNA species: the genome, its exact complement (the antigenome), and a polyadenylated mRNA that acts as a template for the small delta antigen (δAg), the only protein of HDV and essential for genome replication. In a recently reported experimental system, addition of tetracycline induced synthesis of a DNA-directed source of δAg, producing within 24 h a significant increase in accumulation of newly transcribed and processed HDV RNAs. This induction was used here to study the action of various inhibitors on accumulation. For example, potent and HDV-specific inhibition, in the absence of detected host toxicity, could be obtained with ribavirin, mycophenolic acid, and viramidine. An interpretation is that these inhibitors reduced the available GTP pool, leading to a specific inhibition of the synthesis and accumulation of HDV RNA-directed RNA species. In contrast, no inhibition was observed with l -FMAU (2′-fluoro-5-methyl-β- l -arabinofuranosyl-uridine), alpha interferon, or pegylated alpha interferon. After modifications to the experimental system, it was also possible to examine the effects of three known host RNA polymerase inhibitors on HDV genome replication: amanitin, 5,6-dichloro-1-β- d -ribofuranosylbenzimidazole (DRB), and actinomycin. Of most interest, amanitin at low doses blocked accumulation of HDV RNA-directed mRNA but had less effect on HDV genomic and antigenomic RNAs. Additional experiments indicated that this apparent resistance to amanitin inhibition of genomic and antigenomic RNA relative to mRNA may not reflect a difference in the transcribing polymerase but rather relative differences in the processing and stabilization of nascent RNA transcripts.

Metrics

8 Record Views
22 citations in Web of Science
21 citations in Scopus

Details

UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

InCites Highlights

Data related to this publication, from InCites Benchmarking & Analytics tool:

Web of Science research areas
Virology
Logo image