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Viruses 2017, 9(11), 350; doi:10.3390/v9110350

The Role of Infected Cell Proliferation in the Clearance of Acute HBV Infection in Humans

1
Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545, USA
2
Laboratório de Biomatemática, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisboa, Portugal
*
Author to whom correspondence should be addressed.
Received: 25 September 2017 / Revised: 14 November 2017 / Accepted: 16 November 2017 / Published: 18 November 2017
(This article belongs to the Special Issue Mathematical Modeling of Viral Infections)
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Abstract

Around 90–95% of hepatitis B virus (HBV) infected adults do not progress to the chronic phase and, instead, recover naturally. The strengths of the cytolytic and non-cytolytic immune responses are key players that decide the fate of acute HBV infection. In addition, it has been hypothesized that proliferation of infected cells resulting in uninfected progeny and/or cytokine-mediated degradation of covalently closed circular DNA (cccDNA) leading to the cure of infected cells are two major mechanisms assisting the adaptive immune response in the clearance of acute HBV infection in humans. We employed fitting of mathematical models to human acute infection data together with physiological constraints to investigate the role of these hypothesized mechanisms in the clearance of infection. Results suggest that cellular proliferation of infected cells resulting in two uninfected cells is required to minimize the destruction of the liver during the clearance of acute HBV infection. In contrast, we find that a cytokine-mediated cure of infected cells alone is insufficient to clear acute HBV infection. In conclusion, our modeling indicates that HBV clearance without lethal loss of liver mass is associated with the production of two uninfected cells upon proliferation of an infected cell. View Full-Text
Keywords: hepatitis B virus; hepatocyte turnover; cytokine-mediated cure of infected cells; cellular proliferation hepatitis B virus; hepatocyte turnover; cytokine-mediated cure of infected cells; cellular proliferation
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Goyal, A.; Ribeiro, R.M.; Perelson, A.S. The Role of Infected Cell Proliferation in the Clearance of Acute HBV Infection in Humans. Viruses 2017, 9, 350.

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