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Evolution of Hepatitis Delta Virus RNA Genome following Long-Term Replication in Cell Culture
Journal article   Open access   Peer reviewed

Evolution of Hepatitis Delta Virus RNA Genome following Long-Term Replication in Cell Culture

Jinhong Chang, Severin O. Gudima and John M. Taylor
Journal of virology, v 79(21), pp 13310-13316
01 Nov 2005
DOI: https://doi.org/10.1128/JVI.79.21.13310-13316.2005
PMID: 16227253
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1373/clinchem.2005.052241View
Published, Version of Record (VoR)Open Access (License Unspecified),  Open

Abstract

Genetic Diversity and Evolution
Previous studies have defined a novel cell culture system in which a modified RNA genome of hepatitis delta virus (HDV) is able to maintain a low level of continuous replication for at least 1 year, using a separate and limited DNA-directed source of mRNA for the essential small delta protein. This mode of replication is analogous to that used by plant viroids. An examination was made of the nucleotide changes that accumulated on the HDV RNA during 1 year of replication. The length of the RNA genome was maintained, except for some single-nucleotide deletions and insertions. There was an abundance of single-nucleotide substitutions, with a 22-fold excess of these being base transitions rather than transversions. Of the detected transitions, at least 70% were consistent with being the consequences of posttranscriptional RNA editing by an adenosine deaminase acting on RNA. The remainder of the changes, including the single-nucleotide insertions and deletions, are likely to be the consequence of misincorporation during transcription. In addition, an intermolecular competition assay was used to show that the majority of the genomes present after 1 year of replication were essentially as competent in replication as the original single HDV RNA sequence that was used to initiate the genome replication. A model is provided to explain how, in this experimental system, the observed single-nucleotide changes were essentially neutral in terms of their effect on the ability of the HDV genome to carry out continued rounds of replication.

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20 citations in Web of Science
21 citations in Scopus

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Web of Science research areas
Virology
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