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

Goyal, Ashish; Ribeiro, Ruy Miguel; Perelson, Alan S.

doi:10.3390/v9110350

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

Journal Article · Sat Nov 18 00:00:00 EST 2017 · Viruses

DOI:https://doi.org/10.3390/v9110350· OSTI ID:1410624

Goyal, Ashish ^[1]; ^[2]; Perelson, Alan S. ^[1]

Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Faculdade de Medicina de Univ. de Lisboa, Lisboa (Portugal)

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.

View Accepted Manuscript (DOE)

Research Organization:: Los Alamos National Laboratory (LANL)

Sponsoring Organization:: National Institutes of Health; USDOE

Grant/Contract Number:: AC52-06NA25396

OSTI ID:: 1410624

Report Number(s):: LA-UR-17-28723

Journal Information:: Viruses, Journal Name: Viruses Journal Issue: 11 Vol. 9; ISSN VIRUBR; ISSN 1999-4915

Publisher:: MDPICopyright Statement

Country of Publication:: United States

Language:: English

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