Detection of clonally expanded hepatocytes in chimpanzees with chronic hepatitis B virus infection

Mason, William S., Low, Huey-Chi, Xu, Chunxiao, Aldrich, Carol E., Scougall, Catherine A., Grosse, Arend, Clouston, Andrew, Chavez, Deborah, Litwin, Samuel, Peri, Suraj, Jilbert, Allison R. and Lanford, Robert E. (2009) Detection of clonally expanded hepatocytes in chimpanzees with chronic hepatitis B virus infection. Journal of Virology, 83 17: 8396-8408. doi:10.1128/JVI.00700-09

Author Mason, William S.
Low, Huey-Chi
Xu, Chunxiao
Aldrich, Carol E.
Scougall, Catherine A.
Grosse, Arend
Clouston, Andrew
Chavez, Deborah
Litwin, Samuel
Peri, Suraj
Jilbert, Allison R.
Lanford, Robert E.
Title Detection of clonally expanded hepatocytes in chimpanzees with chronic hepatitis B virus infection
Journal name Journal of Virology   Check publisher's open access policy
ISSN 0022-538X
Publication date 2009-09-01
Sub-type Article (original research)
DOI 10.1128/JVI.00700-09
Open Access Status DOI
Volume 83
Issue 17
Start page 8396
End page 8408
Total pages 13
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Language eng
Subject 0605 Microbiology
1108 Medical Microbiology
1103 Clinical Sciences
Formatted abstract
During a hepadnavirus infection, viral DNA integrates at a low rate into random sites in the host DNA, producing unique virus-cell junctions detectable by inverse nested PCR (invPCR). These junctions serve as genetic markers of individual hepatocytes, providing a means to detect their subsequent proliferation into clones of two or more hepatocytes. A previous study suggested that the livers of 2.4-year-old woodchucks (Marmota monax) chronically infected with woodchuck hepatitis virus contained at least 100,000 clones of >1,000 hepatocytes (W. S. Mason, A. R. Jilbert, and J. Summers, Proc. Natl. Acad. Sci. USA 102:1139-1144, 2005). However, possible correlations between sites of viral-DNA integration and clonal expansion could not be explored because the woodchuck genome has not yet been sequenced. In order to further investigate this issue, we looked for similar clonal expansion of hepatocytes in the livers of chimpanzees chronically infected with hepatitis B virus (HBV). Liver samples for invPCR were collected from eight chimpanzees chronically infected with HBV for at least 20 years. Fifty clones ranging in size from ~35 to 10,000 hepatocytes were detected using invPCR in 32 liver biopsy fragments (~1 mg) containing, in total, ~3 x 107 liver cells. Based on searching the analogous human genome, integration sites were found on all chromosomes except Y, ~30% in known or predicted genes. However, no obvious association between the extent of clonal expansion and the integration site was apparent. This suggests that the integration site per se is not responsible for the outgrowth of large clones of hepatocytes.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 29 times in Thomson Reuters Web of Science Article | Citations
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Created: Fri, 04 Sep 2009, 20:21:08 EST