vRNA structured population model for Hepatitis C Virus dynamics.
Improvements in the understanding of the Hepatitis C Virus (HCV) life-cycle have led to the identification of targets and the development of drugs affecting the intracellular reproduction of the virus. These advancements have presented new modeling challenges as the classic models have focused on describing the macroscopic viral kinetics only. Our primary objective is to apply the existing theory of Physiologically Structured Population (PSP) modeling to describe dynamics of viral RNA (vRNA) in infected hepatocytes of patients receiving treatment with Direct-acting Antiviral Agents (DAA). Using vRNA as a physiological structure this work expands on previous structured population models allowing exploration of micro- and macroscopic implications of such treatments. The PSP model provides a description of vRNA distribution in the infected cells at steady state and its time evolution following treatment. The long term behavior of the model predicts viral load time courses in plasma and permits to quantify conditions for the virus eradication. Finally, we demonstrate that PSP models can account for additional structures, which are essential for the viral replication process with potentially far reaching implications in our understanding of HCV infections and treatment options.
Janssen R&D, a division of Janssen Pharmaceutica NV, Turnhoutseweg 30, B-2340 Beerse, Belgium. Electronic address: xwootdet@its.jnj.com.
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Woot de Trixhe
University at Buffalo, Buffalo, NY 14214, United States. Electronic address: wk@buffalo.edu.
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Krzyzanski
Janssen R&D, a division of Janssen Pharmaceutica NV, Turnhoutseweg 30, B-2340 Beerse, Belgium. Electronic address: fdridder@its.jnj.com.
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De Ridder
Janssen R&D, a division of Janssen Pharmaceutica NV, Turnhoutseweg 30, B-2340 Beerse, Belgium. Electronic address: avermeul@its.jnj.com.
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Vermeulen
D000998:Antiviral Agents / Q000627:therapeutic use; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology*; D006526:Hepatitis C / Q000188:drug therapy / Q000821:virology*; D022781:Hepatocytes / Q000821:virology; D006801:Humans; D008954:Models, Biological; D012367:RNA, Viral / Q000302:isolation & purification*; D019562:Viral Load; D014779:Virus Replication
D000998:Antiviral Agents; D012367:RNA, Viral
Direct acting antiviral; Hepatitis C; Physiologically Structured Population model; Viral RNA; Viral kinetics model