Mathematical Models of Early Hepatitis B Virus Dynamics in Humanized Mice

Stanca M. Ciupe, Harel Dahari, Alexander Ploss

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Analyzing the impact of the adaptive immune response during acute hepatitis B virus (HBV) infection is essential for understanding disease progression and control. Here we developed mathematical models of HBV infection which either lack terms for adaptive immune responses, or assume adaptive immune responses in the form of cytolytic immune killing, non-cytolytic immune cure, or non-cytolytic-mediated block of viral production. We validated the model that does not include immune responses against temporal serum hepatitis B DNA (sHBV) and temporal serum hepatitis B surface-antigen (HBsAg) experimental data from mice engrafted with human hepatocytes (HEP). Moreover, we validated the immune models against sHBV and HBsAg experimental data from mice engrafted with HEP and human immune system (HEP/HIS). As expected, the model that does not include adaptive immune responses matches the observed high sHBV and HBsAg concentrations in all HEP mice. By contrast, while all immune response models predict reduction in sHBV and HBsAg concentrations in HEP/HIS mice, the Akaike Information Criterion cannot discriminate between non-cytolytic cure (resulting in a class of cells refractory to reinfection) and antiviral block functions (of up to 99% viral production 1–3 weeks following peak viral load). We can, however, reject cytolytic killing, as it can only match the sHBV and HBsAg data when we predict unrealistic levels of hepatocyte loss.

Original languageEnglish (US)
Article number53
JournalBulletin of Mathematical Biology
Volume86
Issue number5
DOIs
StatePublished - May 2024

All Science Journal Classification (ASJC) codes

  • General Neuroscience
  • Immunology
  • General Mathematics
  • General Biochemistry, Genetics and Molecular Biology
  • General Environmental Science
  • Pharmacology
  • General Agricultural and Biological Sciences
  • Computational Theory and Mathematics

Keywords

  • HBsAg
  • HBV
  • Humanized mice
  • Mathematical modeling

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