Abstract:
:We determined the frequency of integrated viral DNA in the livers of three woodchucks chronically infected with the woodchuck hepatitis virus before and during 30 weeks of therapy with the nucleoside analog L-FMAU [1-(2-fluoro-5-methyl-beta, L-arabinofuranosyl)uracil, clevudine]. We found that although viral covalently closed circular DNA declined 20- to 100-fold, integrated viral DNA showed no discernable decrease over the course of treatment. Thus, chemotherapeutic clearance of covalently closed circular DNA did not involve the replacement of the infected hepatocyte population with uninfected progenitors, but rather, uninfected hepatocytes in the treated liver were derived from the infected hepatocyte population. The frequency of integrated DNA in chronically infected woodchucks was found to be 1 or 2 orders of magnitude higher than that in transiently infected woodchucks, implying that integration and other genomic damage accumulate over the duration of infection. Our results indicate that genetic changes from this damage remain in the liver even while virus infection is cleared and argue for early antiviral intervention in chronic hepatitis.
journal_name
Proc Natl Acad Sci U S Aauthors
Summers J,Mason WSdoi
10.1073/pnas.0307422100keywords:
subject
Has Abstractpub_date
2004-01-13 00:00:00pages
638-40issue
2eissn
0027-8424issn
1091-6490pii
0307422100journal_volume
101pub_type
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