Dynamics of hepatitis B virus clearance in chimpanzees

Proc Natl Acad Sci U S A. 2005 Dec 6;102(49):17780-5. doi: 10.1073/pnas.0508913102. Epub 2005 Nov 23.

Abstract

Mathematical modeling was performed to test the extent to which cytopathic and noncytopathic T cell effector functions contribute to resolution of hepatitis B virus (HBV) infection in three acutely infected chimpanzees. Simulations based exclusively on cytopathic functions show a poor fit to the data and would require the destruction and regeneration of approximately 11 livers for clearance to occur. In contrast, a simulation based on a combination of cytopathic and noncytopathic functions provided a significantly better fit to the data (P < 0.001) and required as much as 5-fold less destruction to clear the virus from the liver. The best fit simulation supports the notion that during the early phase of HBV clearance, noncytopathic T cell effector mechanisms inhibit viral replication and greatly shorten the half-life of the long lived covalently closed circular viral DNA transcriptional template, thereby limiting the extent to which cytopathic T cell effector functions and tissue destruction are required to terminate acute HBV infection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Cytokines / blood
  • Cytotoxicity, Immunologic / immunology
  • Hepatitis B / blood
  • Hepatitis B / immunology*
  • Hepatitis B / virology*
  • Hepatitis B virus / immunology*
  • Pan troglodytes / blood
  • Pan troglodytes / immunology*
  • Pan troglodytes / virology*
  • T-Lymphocytes / immunology

Substances

  • Cytokines