Abstract:
:Chronic hepatitis B affects over 300 million people who are at risk of developing liver cancer. The basis for the persistence of hepatitis B virus (HBV) in hepatocytes, even in the presence of available antiviral therapies, lies in the accumulation of covalently closed circular DNA (cccDNA) in nuclei of infected cells. While methods for cccDNA quantification from liver biopsy specimens and cell lines expressing the virus are known, information about cccDNA formation, stability, and turnover is lacking. In particular, little is known about the fate of cccDNA during cell division. To fill the gaps in knowledge concerning cccDNA biology, we have developed a fluorescence imaging in situ hybridization (FISH)-based assay for the detection of duck hepatitis B virus (DHBV) cccDNA and HBV nuclear DNA in established cell lines. Using FISH, we determined the distribution of cccDNA under conditions mimicking chronic infections with and without antiviral therapy, which prevents de novo viral replication. Our results showed that the copy numbers of viral nuclear DNA can vary by as much as 1.8 orders of magnitude among individual cells and that antiviral therapy leads to a reduction in nuclear DNA in a manner consistent with symmetrical distribution of viral DNA to daughter cells.IMPORTANCE A mechanistic understanding of the stability of HBV cccDNA in the presence of antiviral therapy and during cell division induced by immune-mediated lysis of infected hepatocytes will be critical for the future design of curative antiviral therapies against chronic hepatitis B. Current knowledge about cccDNA stability was largely derived from quantitative analyses of cccDNA levels present in liver samples, and little was known about the fate of cccDNA in individual cells. The development of a FISH-based assay for cccDNA tracking provided the first insights into the fate of DHBV cccDNA and nuclear HBV DNA under conditions mimicking antiviral therapy.
journal_name
J Viroljournal_title
Journal of virologyauthors
Li M,Sohn JA,Seeger Cdoi
10.1128/JVI.01391-17subject
Has Abstractpub_date
2017-12-14 00:00:00issue
1eissn
0022-538Xissn
1098-5514pii
JVI.01391-17journal_volume
92pub_type
杂志文章abstract::Polyacrylamide gel electrophoretic analysis of purified preparations of human and calf diarrhea viruses indicated eight polypeptide components, or possibly nine in the case of the calf diarrhea virus. Thermal denaturation and analytical studies of the calf diarrhea virus genome showed it to consist of 11 double-strand...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.16.5.1229-1235.1975
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journal_title:Journal of virology
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doi:10.1128/JVI.68.9.5882-5889.1994
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.11.6357-6364.1993
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.60.2.423-430.1986
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journal_title:Journal of virology
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.11.7603-7608.1994
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.5.2869-2872.1995
更新日期:1995-05-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:2020-12-09 00:00:00
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pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00381-07
更新日期:2007-11-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.4.1996-2001.2001
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journal_title:Journal of virology
pub_type: 杂志文章
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journal_title:Journal of virology
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.2.9.937-943.1968
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journal_title:Journal of virology
pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.10.6322-6326.1993
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journal_title:Journal of virology
pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:2015-12-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:2006-04-01 00:00:00
abstract::The H-DNA repeat unit of Herpesvirus saimiri strain 11 was cloned in plasmid vector pAGO, and the nucleotide sequence was determined by the dideoxy chain termination method. One unit of repetitive DNA has 1,444 base pairs with 70.8% G+C content. The structural features of repeat DNA sequences at the termini of intact ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.55.1.133-139.1985
更新日期:1985-07-01 00:00:00
abstract::Resistance or susceptibility of various mouse strains to central nervous system disease caused by different strains of coronavirus is well known. Data from the present study draw attention to an additional, genetically determined mechanism controlling CV infections. The resistance to A59 and JHM virus (JHMV) associate...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.62.9.3371-3377.1988
更新日期:1988-09-01 00:00:00