Deep sequencing of liver explant transcriptomes reveals extensive expression from integrated hepatitis B virus DNA
Autor: | Kristoffer Hellstrand, Johan Ringlander, Ka-Wei Tang, Simon B. Larsson, Helene Norder, Catarina Skoglund, Gustaf E. Rydell, Maria Castedal, Magnus Lindh, Sanna Abrahamsson, Kasthuri Prakash, Maria Andersson |
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Rok vydání: | 2020 |
Předmět: |
Hepatitis B virus
HBsAg Carcinoma Hepatocellular Biology medicine.disease_cause Deep sequencing 03 medical and health sciences Liver disease Hepatitis B Chronic 0302 clinical medicine Virology medicine Humans 030212 general & internal medicine Hepatitis B Surface Antigens Hepatology Liver Neoplasms High-Throughput Nucleotide Sequencing virus diseases cccDNA Hepatitis B medicine.disease digestive system diseases Infectious Diseases Liver Hepatocellular carcinoma DNA Viral 030211 gastroenterology & hepatology Human genome Hepatitis D virus Transcriptome |
Zdroj: | Journal of Viral Hepatitis. 27:1162-1170 |
ISSN: | 1365-2893 1352-0504 |
Popis: | 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. |
Databáze: | OpenAIRE |
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