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Journal of Virology, February 2000, p. 1495-1505, Vol. 74, No. 3
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Apoptosis and Regeneration of Hepatocytes during Recovery from Transient Hepadnavirus Infections

Ju-Tao Guo, Huan Zhou, Chen Liu, Carol Aldrich, Jeffrey Saputelli, Tony Whitaker, M. Inmaculada Barrasa, William S. Mason, and Christoph Seeger*

Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111

Received 23 June 1999/Accepted 3 November 1999

It is well known that hepatitis B virus infections can be transient or chronic, but the basis for this dichotomy is not known. To gain insight into the mechanism responsible for the clearance of hepadnavirus infections, we have performed a molecular and histologic analysis of liver tissues obtained from transiently infected woodchucks during the critical phase of the recovery period. We found as expected that clearance from transient infections occurred subsequent to the appearance of CD4+ and CD8+ T cells and the production of interferon gamma and tumor necrosis factor alpha in the infected liver. These events were accompanied by a significant increase in apoptosis and regeneration of hepatocytes. Surprisingly, however, accumulation of virus-free hepatocytes was delayed for several weeks following this initial influx of lymphocytes. In addition, we observed that chronically infected animals can exhibit levels of T-cell accumulation, cytokine expression, and apoptosis that are comparable with those observed during the initial phase of transient infections. Our results are most consistent with a model for recovery predicting replacement of infected hepatocytes with regenerated cells, which by unknown mechanisms remain protected from reinfection in animals that can be cured.

* Corresponding author. Mailing address: Institute for Cancer Research, Fox Chase Cancer Center, 7701 Burholme Ave., Philadelphia, PA 19111. Phone: (215) 728-4312. Fax: (215) 728-4329. E-mail: c_seeger{at}fccc.edu.

Journal of Virology, February 2000, p. 1495-1505, Vol. 74, No. 3
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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