Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/16051
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dc.contributor.authorBetz-Stablein, BD-
dc.contributor.authorTöpfer, A-
dc.contributor.authorLittlejohn, M-
dc.contributor.authorYuen, L-
dc.contributor.authorColledge, D-
dc.contributor.authorSozzi, V-
dc.contributor.authorAngus, Peter W-
dc.contributor.authorThompson, A-
dc.contributor.authorRevill, P-
dc.contributor.authorBeerenwinkel, N-
dc.contributor.authorWarner, N-
dc.contributor.authorLuciani, F-
dc.date.accessioned2016-06-21T05:08:08Z-
dc.date.available2016-06-21T05:08:08Z-
dc.date.issued2016-06-01-
dc.identifier.citationJournal of Virology 2016; 90(16): 7171-7183en_US
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/16051-
dc.description.abstractChronic hepatitis B (CHB) is prevalent worldwide. The infectious agent, hepatitis B virus (HBV) replicates via an RNA intermediate and is error-prone, leading to rapid generation of closely related but not identical viral variants, including those that can escape host immune responses and antiviral treatments. The complexity of CHB can be further enhanced by the presence of HBV variants with large deletions in the genome, generated via splicing (spHBV). Although spHBV variants are incapable of autonomous replication, their replication is rescued by wild-type HBV. SpHBV variants have been shown to enhance wild-type virus replication, and their prevalence increases with liver disease progression. Single-molecule deep sequencing was performed on whole HBV genomes extracted from longitudinal samples of a post-liver transplant CHB subject, collected over a 15-year period that included the liver explant. By employing novel bioinformatics methods, this analysis showed a complex dynamics of the viral population across a period of changing treatment regimens. The spHBV detected in the liver explant remained present post-transplantation, along with emergence of a highly diverse novel spHBV population as well as variants with multiple deletions in the preS genes. The identification of novel mutations outside the HBV reverse transcriptase gene that co-occur with known drug resistant mutations, highlight the relevance of using full genome deep sequencing and support the hypothesis that drug resistance involves interactions across the full-length HBV genome. IMPORTANCE: Single-molecule sequencing allowed characterising, in unprecedented detail, the evolution of HBV populations and offered unique insights into the dynamics of defective and spHBV variants following liver transplantation and complex treatment regimes. This analysis also showed rapid adaptation of HBV populations to treatment regimens with evolving drug resistance phenotypes and evidence of purifying selection across the whole genome. Finally, the new open source bioinformatics tools are freely available, with the capacity to easily identify potential spliced variants from deep sequencing data.en_US
dc.titleSingle-molecule sequencing reveals complex genomic variation of hepatitis B virus during 15 years of chronic infection following liver transplantationen_US
dc.typeJournal Articleen_US
dc.identifier.journaltitleJournal of Virologyen_US
dc.identifier.affiliationSystems Medicine, School of Medical Sciences, Faculty of Medicine, University of New South Wales, Australiaen_US
dc.identifier.affiliationVictorian Infectious Disease Reference Laboratory (VIDRL), Melbourne, Australiaen_US
dc.identifier.affiliationDepartment of Gastroenterology, St Vincent Hospital, Melbourne.en_US
dc.identifier.affiliationDepartment of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland SIB Swiss Institute of Bioinformatics, Basel, Switzerland.en_US
dc.identifier.affiliationMedicine (University of Melbourne)en_US
dc.identifier.pubmedurihttps://pubmed.ncbi.nlm.nih.gov/27252524en_US
dc.identifier.doi10.1128/JVI.00243-16en_US
dc.type.contentTexten_US
dc.type.austinJournal Articleen_US
local.name.researcherAngus, Peter W
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
item.fulltextNo Fulltext-
item.grantfulltextnone-
item.openairetypeJournal Article-
crisitem.author.deptVictorian Liver Transplant Unit-
crisitem.author.deptGastroenterology and Hepatology-
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