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A Competent Hepatocyte Model Examining Hepatitis B Virus Entry through Sodium Taurocholate Cotransporting Polypeptide as a Therapeutic Target
Published on: May 10, 2022
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A quantitative systems pharmacology model for acute viral hepatitis B
Eduardo Asín-Prieto1,2, Zinnia P Parra-Guillen1,2, José David Gómez Mantilla1,2
1Pharmacometrics & Systems Pharmacology Lab, Department of Pharmaceutical Technology and Chemistry, School of Pharmacy and Nutrition, C/Irunlarrea 1, University of Navarra, Pamplona 31080, Spain.
Computational and Structural Biotechnology Journal
|September 30, 2021
Summary
A new model shows that the immune system
Area of Science:
- * Virology and immunology
- * Systems pharmacology
- * Infectious disease modeling
Background:
- * Hepatitis B virus (HBV) infection poses a significant global health challenge, particularly when it becomes chronic.
- * Most adult HBV infections resolve, but understanding the immune response is key to preventing chronicity.
- * Early life infections have a high rate of progression to chronic hepatitis B.
Purpose of the Study:
- * To develop a quantitative systems pharmacology model for acute hepatitis B.
- * To characterize HBV dynamics and immune responses (innate, adaptive, tolerant).
- * To identify key biological processes involved in HBV infection resolution and chronicity.
Main Methods:
- * Integrated data from multiple sources across different organizational levels.
- * Developed a mechanistic framework for HBV dynamics and immune interactions.
- * Validated the model against clinical data from acute hepatitis B patients.
Main Results:
- * The model accurately describes the timeline and plausibility of the immune response to HBV.
- * Demonstrated the negligible role of innate immunity and the critical role of cellular immunity in viral clearance.
- * Identified that reduced cytotoxic CD8+ T-cell proliferation or increased immunoregulatory effects can lead to chronic infection.
Conclusions:
- * The developed model provides a holistic view of acute hepatitis B pathogenesis.
- * Highlights the crucial role of adaptive cellular immunity in resolving HBV infection.
- * Suggests that modulating CD8+ T-cell responses or immunoregulatory pathways could be therapeutic targets to prevent chronic hepatitis B.
Keywords:
AHB, acute hepatitis BALT, alanine aminotransferaseCHB, chronic hepatitis BCTL*, activated CTLCTL, antigen-specific cytotoxic T lymphocytesCTLm, memory CTLDC*, activated dendritic cellsDC, dendritic cellsHB, Hepatitis BHBV, hepatitis B virus, HBV DNA, circulating DNA levels of HBVHBsAg, hepatitis B surface antigenHep, hepatocytesHepatitis BHeptot, total hepatocytesIFN, interferonImmune system dynamicsLN, lymph nodeLPC, long-lived plasma cellsLV, liverMDSC, myeloid-derived suppressor cellsMechanistic modelingNK*, activated NKNK, natural killer cellsODE, ordinary differential equationsPB, plasmablastsPC, plasma cellsPL, plasmaQSP, quantitative systems pharmacologyQuantitative systems pharmacologySPC, short-lived plasma cellsTRAIL, tumor necrosis factor–related apoptosis-inducing ligandTh0, naïve T cellsTreg, regulatory T cellsViral dynamicsanti-HBc, specific antibodies against core hepatitis B antigenanti-HBs, specific antibodies against surface hepatitis B antigendHep, debris hepatocytesiHep, infected hepatocytespDC, plasmacytoid DC
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