Hepatitis delta virus infects the cells of hepadnavirus-induced hepatocellular carcinoma in woodchucks
Hepatitis delta virus (HDV) is a natural subviral agent of human hepatitis B virus (HBV). HDV enhances liver damage during concomitant infection with HBV. The molecular pathogenesis of HDV infection remains poorly understood. To advance our understanding of the relationship between HDV infection and...
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Published in | Hepatology (Baltimore, Md.) Vol. 56; no. 1; pp. 76 - 85 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Hoboken
Wiley Subscription Services, Inc., A Wiley Company
01.07.2012
Wiley Wiley Subscription Services, Inc |
Subjects | |
Online Access | Get full text |
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Summary: | Hepatitis delta virus (HDV) is a natural subviral agent of human hepatitis B virus (HBV). HDV enhances liver damage during concomitant infection with HBV. The molecular pathogenesis of HDV infection remains poorly understood. To advance our understanding of the relationship between HDV infection and liver cancer, it was determined whether HDV could infect in vivo the cells of hepadnavirus‐induced hepatocellular carcinoma (HCC). Woodchucks (Marmota monax) that were chronically infected with HBV‐related woodchuck hepatitis virus (WHV) and already developed HCCs were used as an experimental model. The locations of HCCs within the livers were determined using ultrasound imaging followed by open surgery. One week after surgery the WHV carrier woodchucks were superinfected with WHV‐enveloped HDV (wHDV). Six weeks later the animals were sacrificed and HDV replication in normal liver tissues and in center masses of HCCs was evidenced by Northern analysis, real‐time polymerase chain reaction assay, and immunohistochemistry. Based on accumulation levels of HDV RNAs and numbers of infected cells, the efficiency of wHDV infection appears to be comparable in most HCCs and normal liver tissues. Conclusion: Cells of WHV‐induced HCCs are susceptible to HDV infection in vivo, and therefore express functional putative WHV receptors and support the steps of the attachment/entry governed by the hepadnavirus envelope proteins. Because others previously hypothesized that hepadnavirus‐induced HCCs are resistant to reinfection with a hepadnavirus in vivo, our data suggest that if such a resistance exists it likely occurs via a block at the post‐entry step. The demonstrated ability of HDV to infect already formed HCCs may facilitate development of novel strategies further dissecting the mechanism of liver pathogenesis associated with HDV infection. (HEPATOLOGY 2012;56:76–85) |
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Bibliography: | University of Kansas Endowment Association National Institutes of Health (NIH) - No. NCI R01CA166213; No. NCRR P20RR016443 ArticleID:HEP25663 Potential conflict of interest: Nothing to report. istex:1EEDDD59ED038535193B5E3A898661F46EDFC5AC ark:/67375/WNG-8ZNS85FS-M fax: 913‐588‐7295 ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0270-9139 1527-3350 |
DOI: | 10.1002/hep.25663 |