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

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. Lastly, 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.
Authors:
 [1] ; ORCiD logo [2] ;  [1]
  1. Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
  2. Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Faculdade de Medicina de Univ. de Lisboa, Lisboa (Portugal)
Publication Date:
Report Number(s):
LA-UR-17-28723
Journal ID: ISSN 1999-4915; VIRUBR
Grant/Contract Number:
AC52-06NA25396
Type:
Accepted Manuscript
Journal Name:
Viruses
Additional Journal Information:
Journal Volume: 9; Journal Issue: 11; Journal ID: ISSN 1999-4915
Publisher:
MDPI
Research Org:
Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Sponsoring Org:
National Institutes of Health (NIH); USDOE
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; 59 BASIC BIOLOGICAL SCIENCES; Biological Science; hepatitis B virus; hepatocyte turnover; cytokine-mediated cure of infected cells; cellular proliferation
OSTI Identifier:
1410624