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Restoration in vivo of defective hepatitis delta virus RNA genomes
Journal article   Open access   Peer reviewed

Restoration in vivo of defective hepatitis delta virus RNA genomes

Severin O Gudima, Jinhong Chang and John M Taylor
RNA (Cambridge), v 12(6), pp 1061-1073
Jun 2006
DOI: https://doi.org/10.1261/rna.2328806
PMID: 16618966
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.7759/cureus.45415View
Published, Version of Record (VoR)Maybe Open Access (Publisher Bronze),  Open
url
https://doi.org/10.1261/rna.2328806View
Published, Version of Record (VoR) Open

Abstract

Base Pairing Base Sequence Cloning, Molecular Genome, Viral Hepatitis Delta Virus - genetics Hepatitis Delta Virus - physiology Humans Models, Biological Models, Genetic Molecular Sequence Data Mutagenesis, Insertional Mutation RNA Polymerase II - genetics RNA Polymerase II - metabolism RNA Precursors - metabolism RNA Processing, Post-Transcriptional RNA, Viral - biosynthesis Sequence Analysis Transcription, Genetic Transfection Tumor Cells, Cultured Virus Replication
The 1679-nt single-stranded RNA genome of hepatitis delta virus (HDV) is circular in conformation. It is able to fold into an unbranched rodlike structure via intramolecular base-pairing. This RNA is replicated by host RNA polymerase II (Pol II). Such transcription is unique, because Pol II is known only for its ability to act on DNA templates. The present study addressed the ability of the HDV RNA replication to tolerate insertions of up to 1000 nt of non-HDV sequence either at an end of the rodlike RNA structure or at a site embedded within the rod. The insertions did not interfere with the ability of primary transcripts to be processed in vivo by ribozyme cleavage and ligation. The insertions greatly reduced the ability of genomes to replicate. However, when total RNA from such transfected cells was used to transfect new recipient cells, replicating HDV RNAs could be detected by Northern analyses. The size of the emerged RNAs was consistent with loss of the inserted sequences. RT-PCR, cloning, and sequencing showed that recovery involved removal of inserted sequences with or without small deletions of adjacent RNA sequences. Such restoration of the RNA genome is consistent with a model requiring intramolecular template-switching (RNA recombination) during RNA-directed transcription, in combination with biological selection for maintenance of the rodlike structure of the template.

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4 citations in Web of Science
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UN Sustainable Development Goals (SDGs)

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#3 Good Health and Well-Being

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Web of Science research areas
Biochemistry & Molecular Biology
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