Dynamics of hepatitis B virus clearance in chimpanzees.
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.
Murray
John M
JM
School of Mathematics, University of New South Wales, Sydney NSW 2052, Australia.
Wieland
Stefan F
SF
Purcell
Robert H
RH
Chisari
Francis V
FV
D000208:Acute Disease; D000818:Animals; D016207:Cytokines / Q000097:blood; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D006509:Hepatitis B / Q000097:blood / Q000276:immunology* / Q000821:virology*; D006515:Hepatitis B virus / Q000276:immunology*; D002679:Pan troglodytes / Q000097:blood / Q000276:immunology* / Q000821:virology*; D013601:T-Lymphocytes / Q000276:immunology
D016207:Cytokines