Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 102, Issue 49, Pages 17780-17785Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0508913102
Keywords
mathematical modeling; pathogenesis; covalently closed circular DNA
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Funding
- NIAID NIH HHS [R01 AI020001, AI20001] Funding Source: Medline
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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 approximate to 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.
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