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 pro...
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| Format: | Article |
| Language: | English |
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MDPI AG
2017-11-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/9/11/350 |
| _version_ | 1818133317047812096 |
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| author | Ashish Goyal Ruy M. Ribeiro Alan S. Perelson |
| author_facet | Ashish Goyal Ruy M. Ribeiro Alan S. Perelson |
| author_sort | Ashish Goyal |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T08:50:48Z |
| format | Article |
| id | doaj.art-b00ca555a5ff44709b667c52c0805e67 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-12-11T08:50:48Z |
| publishDate | 2017-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-b00ca555a5ff44709b667c52c0805e672022-12-22T01:14:02ZengMDPI AGViruses1999-49152017-11-0191135010.3390/v9110350v9110350The Role of Infected Cell Proliferation in the Clearance of Acute HBV Infection in HumansAshish Goyal0Ruy M. Ribeiro1Alan S. Perelson2Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545, USATheoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545, USATheoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545, USAAround 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.https://www.mdpi.com/1999-4915/9/11/350hepatitis B virushepatocyte turnovercytokine-mediated cure of infected cellscellular proliferation |
| spellingShingle | Ashish Goyal Ruy M. Ribeiro Alan S. Perelson The Role of Infected Cell Proliferation in the Clearance of Acute HBV Infection in Humans Viruses hepatitis B virus hepatocyte turnover cytokine-mediated cure of infected cells cellular proliferation |
| title | The Role of Infected Cell Proliferation in the Clearance of Acute HBV Infection in Humans |
| title_full | The Role of Infected Cell Proliferation in the Clearance of Acute HBV Infection in Humans |
| title_fullStr | The Role of Infected Cell Proliferation in the Clearance of Acute HBV Infection in Humans |
| title_full_unstemmed | The Role of Infected Cell Proliferation in the Clearance of Acute HBV Infection in Humans |
| title_short | The Role of Infected Cell Proliferation in the Clearance of Acute HBV Infection in Humans |
| title_sort | role of infected cell proliferation in the clearance of acute hbv infection in humans |
| topic | hepatitis B virus hepatocyte turnover cytokine-mediated cure of infected cells cellular proliferation |
| url | https://www.mdpi.com/1999-4915/9/11/350 |
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