A mathematical model of the intracellular replication and within host evolution of hepatitis type B virus: Understanding the long time course of chronic hepatitis

Nakabayashi J & Sasaki A (2011). A mathematical model of the intracellular replication and within host evolution of hepatitis type B virus: Understanding the long time course of chronic hepatitis. Journal of Theoretical Biology 269 (1): 318-329. DOI:10.1016/j.jtbi.2010.10.024.

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Abstract

Hepatitis B virus (HBV) causes acute and chronic liver disease. Especially, chronic hepatitis is a major risk factor of liver cirrhosis and hepatocellular carcinoma. Viral kinetics of HBV observed in peripheral blood is quite different depending on the clinical course of hepatitis. But the relationship between the intracellular replication dynamics and clinical course of HBV infection is unclear. Further it is very difficult to predict the long time course of hepatitis because the nature of HBV is changed by mutation within host with high mutation rate. We investigate the intracellular replication dynamics and within host evolution of HBV by using a mathematical model. Two different intracellular replication patterns of HBV, "explosive" and "arrested", are switched depending on the viral gene expression pattern. In the explosive replication, prominent growth of HBV is observed. On the other hand, the virion production is restricted in the arrested replication. It is suggested that the arrested and explosive replication is associated with chronic hepatitis and exacerbation of hepatitis respectively. It is shown by our evolutionary simulation that the exacerbation of hepatitis is caused by the emergence of explosive genotype of HBV from arrested genotype by mutation during chronic hepatitis. It is also shown that chronic infection without exacerbation is maintained by short waiting time for virion release and superinfection with arrested genotype. It is suggested that extension of waiting time for virion release and existence of uninfected hepatocyte in the liver may become risk factors for the exacerbation of hepatitis.

Item Type: Article
Uncontrolled Keywords: HBV; Acute and chronic hepatitis; Intracellular dynamics; Within host evolution
Research Programs: Evolution and Ecology (EEP)
Bibliographic Reference: Journal of Theoretical Biology; 269(1):318-329 (21 January 2011) (Published online 9 November 2010)
Depositing User: IIASA Import
Date Deposited: 15 Jan 2016 08:45
Last Modified: 24 Feb 2016 15:15
URI: http://pure.iiasa.ac.at/9656

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