A quantitative systems pharmacology model for acute viral hepatitis B
| Autor: | Iñaki F. Trocóniz, Juan Jose Perez-Ruixo, Xavier Woot de Trixhe, Eduardo Asín-Prieto, Kim Stuyckens, Zinnia P. Parra-Guillen, José David Gómez Mantilla, Joris Vandenbossche |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Mechanistic modeling
Disease dHep debris hepatocytes medicine.disease_cause Biochemistry LPC long-lived plasma cells Immune system dynamics Structural Biology DC dendritic cells PB plasmablasts Medicine QSP quantitative systems pharmacology Liver infection TRAIL tumor necrosis factor–related apoptosis-inducing ligand Th0 naïve T cells Hepatitis B Computer Science Applications CTL antigen-specific cytotoxic T lymphocytes HBsAg hepatitis B surface antigen anti-HBc specific antibodies against core hepatitis B antigen anti-HBs specific antibodies against surface hepatitis B antigen CTL* activated CTL HB Hepatitis B iHep infected hepatocytes Viral dynamics ODE ordinary differential equations CHB chronic hepatitis B Biotechnology Systems pharmacology Research Article NK* activated NK pDC plasmacytoid DC PL plasma SPC short-lived plasma cells Biophysics Heptot total hepatocytes Virus NK natural killer cells Quantitative systems pharmacology Immune system PC plasma cells ALT alanine aminotransferase Genetics CTLm memory CTL Hep hepatocytes IFN interferon DC* activated dendritic cells HBV hepatitis B virus HBV DNA circulating DNA levels of HBV MDSC myeloid-derived suppressor cells ComputingMethodologies_COMPUTERGRAPHICS Hepatitis B virus AHB acute hepatitis B business.industry LV liver medicine.disease Treg regulatory T cells Immunology LN lymph node business TP248.13-248.65 CD8 |
| Zdroj: | Computational and Structural Biotechnology Journal Computational and Structural Biotechnology Journal, Vol 19, Iss, Pp 4997-5007 (2021) |
| ISSN: | 2001-0370 |
| Popis: | Graphical abstract Highlights • Mechanistic model characterizing acute immune response and HBV system interactions. • Key role of the cellular and regulatory response triggering hepatitis B chronicity. • Modelling framework to easily incorporate and explore additional biological mechanisms. Hepatitis B liver infection is caused by hepatitis B virus (HBV) and represents a major global disease problem when it becomes chronic, as is the case for 80–90% of vertical or early life infections. However, in the vast majority (>95%) of adult exposures, the infected individuals are capable of mounting an effective immune response leading to infection resolution. A good understanding of HBV dynamics and the interaction between the virus and immune system during acute infection represents an essential step to characterize and understand the key biological processes involved in disease resolution, which may help to identify potential interventions to prevent chronic hepatitis B. In this work, a quantitative systems pharmacology model for acute hepatitis B characterizing viral dynamics and the main components of the innate, adaptive, and tolerant immune response has been successfully developed. To do so, information from multiple sources and across different organization levels has been integrated in a common mechanistic framework. The final model adequately describes the chronology and plausibility of an HBV-triggered immune response, as well as clinical data from acute patients reported in the literature. Given the holistic nature of the framework, the model can be used to illustrate the relevance of the different immune pathways and biological processes to ultimate response, observing the negligible contribution of the innate response and the key contribution of the cellular response on viral clearance. More specifically, moderate reductions of the proliferation of activated cytotoxic CD8+ lymphocytes or increased immunoregulatory effects can drive the system towards chronicity. |
| Databáze: | OpenAIRE |
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