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Deep Sequencing of Liver Explant Transcriptomes Reveals Extensive Expression From Integrated Hepatitis B Virus DNA
Johan Ringlander 1 , Catarina Skoglund 2 3 , Kasthuri Prakash 1 , Maria E Andersson 1 , Simon B Larsson 1 , Ka-Wei Tang 1 , Gustaf E Rydell 1 , Sanna Abrahamsson 4 , Maria Castedal 2 3 , Heléne Norder 1 , Kristoffer Hellstrand 1 , Magnus Lindh 1
Affiliations
Affiliations
1
Department of Infectious Diseases, Institute for Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
2
The Transplant Institute, Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden.
3
Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
4
Bioinformatics Core Facility, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
PMID: 32592629 DOI: 10.1111/jvh.13356
Abstract
Hepatitis B virus (HBV) is a major cause of hepatocellular carcinoma (HCC). Integration of HBV DNA into the human genome may contribute to oncogenesis and to the production of the hepatitis B surface antigen (HBsAg). Whether integrations contribute to HBsAg levels in the blood is poorly known. Here we characterize the HBV RNA profile of HBV integrations in liver tissue in patients with chronic HBV infection, with or without concurrent hepatitis D infection, by transcriptome deep sequencing. Transcriptomes were determined in liver tissue by deep sequencing providing 200 million reads per sample. Integration points were identified using a bioinformatic pipeline. Explanted liver tissue from five patients with end-stage liver disease caused by HBV or HBV/HDV was studied along with publicly available transcriptomes from 21 patients. Almost all HBV RNA profiles were devoid of reads in the core and the 3' redundancy (nt 1830-1927) regions, and contained a large number of chimeric viral/human reads. Hence HBV transcripts from integrated HBV DNA rather than from covalently closed circular HBV DNA (cccDNA) predominated in late-stage HBV infection, in particular in cases with hepatitis D virus co-infection. The findings support the suggestion that integrated HBV DNA can be a significant source of HBsAg in humans.
Keywords: HBsAg; HCC; hepatitis B virus; integration; transcriptome.
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发表于 2020-6-29 15:14
