Antibody Responses during Hepatitis B Viral Infection

Ciupe, Stanca M.; Ribeiro, Ruy M.; Perelson, Alan S.

doi:10.1371/journal.pcbi.1003730

Title: Antibody Responses during Hepatitis B Viral Infection

Journal Article · Thu Jul 31 00:00:00 EDT 2014 · PLoS Computational Biology (Online)

DOI:https://doi.org/10.1371/journal.pcbi.1003730· OSTI ID:1627236

Ciupe, Stanca M. ^[1]; Ribeiro, Ruy M. ^[2]; Perelson, Alan S. ^[2]

Virginia Polytechnic Inst. and State Univ. (Virginia Tech), Blacksburg, VA (United States). Dept. of Mathematics
Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Division

Hepatitis B is a DNA virus that infects liver cells and can cause both acute and chronic disease. It is believed that both viral and host factors are responsible for determining whether the infection is cleared or becomes chronic. Here we investigate the mechanism of protection by developing a mathematical model of the antibody response following hepatitis B virus (HBV) infection. We fitted the model to data from seven infected adults identified during acute infection and determined the ability of the virus to escape neutralization through overproduction of non-infectious subviral particles, which have HBs proteins on their surface, but do not contain nucleocapsid protein and viral nucleic acids. We showed that viral clearance can be achieved for high anti-HBV antibody levels, as in vaccinated individuals, when: (1) the rate of synthesis of hepatitis B subviral particles is slow; (2) the rate of synthesis of hepatitis B subviral particles is high but either anti-HBV antibody production is fast, the antibody affinity is high, or the levels of pre-existent HBV-specific antibody at the time of infection are high, as could be attained by vaccination. We further showed that viral clearance can be achieved for low equilibrium antiHBV antibody levels, as in unvaccinated individuals, when a strong cellular immune response controls early infection.

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Research Organization:: Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division

Grant/Contract Number:: AC52-06NA25396

OSTI ID:: 1627236

Journal Information:: PLoS Computational Biology (Online), Vol. 10, Issue 7; ISSN 1553-7358

Publisher:: Public Library of ScienceCopyright Statement

Country of Publication:: United States

Language:: English

References (71)

Immunology of hepatitis B virus and hepatitis C virus infection Rehermann, Barbara; Nascimbeni, Michelina Nature Reviews Immunology, Vol. 5, Issue 3 https://doi.org/10.1038/nri1573	journal	March 2005
Virus-neutralizing Antibodies to Hepatitis B Virus: The Nature of an Immunogenic Epitope on the S Gene Peptide Waters, J.; Pignatelli, M.; Galpin, S. Journal of General Virology, Vol. 67, Issue 11 https://doi.org/10.1099/0022-1317-67-11-2467	journal	November 1986
Intracellular Inactivation of the Hepatitis B Virus by Cytotoxic T Lymphocytes Guidotti, Luca G.; Ishikawa, Tetsuya; Hobbs, Monte V. Immunity, Vol. 4, Issue 1 https://doi.org/10.1016/S1074-7613(00)80295-2	journal	January 1996
Interferon prevents formation of replication-competent hepatitis B virus RNA-containing nucleocapsids Wieland, S. F.; Eustaquio, A.; Whitten-Bauer, C. Proceedings of the National Academy of Sciences, Vol. 102, Issue 28 https://doi.org/10.1073/pnas.0504273102	journal	July 2005
The role of cells refractory to productive infection in acute hepatitis B viral dynamics Ciupe, S. M.; Ribeiro, R. M.; Nelson, P. W. Proceedings of the National Academy of Sciences, Vol. 104, Issue 12 https://doi.org/10.1073/pnas.0603626104	journal	March 2007
Viruses, Immunity, and Cancer: Lessons from Hepatitis B Chisari, Francis V. The American Journal of Pathology, Vol. 156, Issue 4 https://doi.org/10.1016/S0002-9440(10)64980-2	journal	April 2000
Kinetics of the immune response during HBV and HCV infection Bertoletti, A. Hepatology, Vol. 38, Issue 1 https://doi.org/10.1053/jhep.2003.50310	journal	July 2003
Correlation of Virus and Host Response Markers with Circulating Immune Complexes during Acute and Chronic Woodchuck Hepatitis Virus Infection Glebe, Dieter; Lorenz, Heike; Gerlich, Wolfram H. Journal of Virology, Vol. 83, Issue 4 https://doi.org/10.1128/JVI.01934-08	journal	December 2008
Host factors involved in hepatitis B virus maturation, assembly, and egress Prange, Reinhild Medical Microbiology and Immunology, Vol. 201, Issue 4 https://doi.org/10.1007/s00430-012-0267-9	journal	September 2012
Viral and cellular determinants involved in hepadnaviral entry Glebe, Dieter World Journal of Gastroenterology, Vol. 13, Issue 1 https://doi.org/10.3748/wjg.v13.i1.22	journal	January 2007
Hepatitis B small surface antigen particles are octahedral Gilbert, R. J. C.; Beales, L.; Blond, D. Proceedings of the National Academy of Sciences, Vol. 102, Issue 41 https://doi.org/10.1073/pnas.0505062102	journal	October 2005
Morphogenesis of hepatitis B virus and its subviral envelope particles Patient, Romuald; Hourioux, Christophe; Roingeard, Philippe Cellular Microbiology, Vol. 11, Issue 11 https://doi.org/10.1111/j.1462-5822.2009.01363.x	journal	November 2009
Viral dynamics in hepatitis B virus infection. Nowak, M. A.; Bonhoeffer, S.; Hill, A. M. Proceedings of the National Academy of Sciences, Vol. 93, Issue 9 https://doi.org/10.1073/pnas.93.9.4398	journal	April 1996
Modelling viral and immune system dynamics Perelson, Alan S. Nature Reviews Immunology, Vol. 2, Issue 1 https://doi.org/10.1038/nri700	journal	January 2002
HIV-1 Dynamics in Vivo: Virion Clearance Rate, Infected Cell Life-Span, and Viral Generation Time Perelson, A. S.; Neumann, A. U.; Markowitz, M. Science, Vol. 271, Issue 5255 https://doi.org/10.1126/science.271.5255.1582	journal	March 1996
Modeling Plasma Virus Concentration during Primary HIV Infection Stafford, Max A.; Corey, Lawrence; Cao, Yunzhen Journal of Theoretical Biology, Vol. 203, Issue 3 https://doi.org/10.1006/jtbi.2000.1076	journal	April 2000
Analysis of hepatitis B viral load decline under potent therapy: Complex decay profiles observed Lewin, S. Hepatology, Vol. 34, Issue 5 https://doi.org/10.1053/jhep.2001.28509	journal	November 2001
Biphasic clearance kinetics of hepatitis B virus from patients during adefovir dipivoxil therapy Tsiang, Manuel; Rooney, James F.; Toole, John J. Hepatology, Vol. 29, Issue 6 https://doi.org/10.1002/hep.510290626	journal	June 1999
Liver Regeneration Michalopoulos, George K.; DeFrances, Marie C. Science, Vol. 276, Issue 5309 https://doi.org/10.1126/science.276.5309.60	journal	April 1997
Modeling the mechanisms of acute hepatitis B virus infection Ciupe, Stanca M.; Ribeiro, Ruy M.; Nelson, Patrick W. Journal of Theoretical Biology, Vol. 247, Issue 1 https://doi.org/10.1016/j.jtbi.2007.02.017	journal	July 2007
Virus dynamics and drug therapy Bonhoeffer, S.; May, R. M.; Shaw, G. M. Proceedings of the National Academy of Sciences, Vol. 94, Issue 13 https://doi.org/10.1073/pnas.94.13.6971	journal	June 1997
13 Modelling the in vivo growth rate of HIV: implications for vaccination Ribeiro, Ruy M.; Dixit, Narendra M.; Perelson, Alan S. Multidisciplinary Approaches to Theory in Medicine https://doi.org/10.1016/S1571-0831(06)80017-1	book	January 2005
Dynamics of hepatitis B virus clearance in chimpanzees Murray, J. M.; Wieland, S. F.; Purcell, R. H. Proceedings of the National Academy of Sciences, Vol. 102, Issue 49 https://doi.org/10.1073/pnas.0508913102	journal	November 2005
Analysis of intrahepatic HBV-specific cytotoxic T-cells during and after acute HBV infection in humans Sprengers, Dave; Molen, Renate G. van der; Kusters, Johannes G. Journal of Hepatology, Vol. 45, Issue 2 https://doi.org/10.1016/j.jhep.2005.12.022	journal	August 2006
Modeling the adaptive immune response in HBV infection Yousfi, Noura; Hattaf, Khalid; Tridane, Abdessamad Journal of Mathematical Biology, Vol. 63, Issue 5 https://doi.org/10.1007/s00285-010-0397-x	journal	January 2011
Use of Laser Capture Microdissection to Map Hepatitis C Virus–Positive Hepatocytes in Human Liver Kandathil, Abraham J.; Graw, Frederik; Quinn, Jeffrey Gastroenterology, Vol. 145, Issue 6 https://doi.org/10.1053/j.gastro.2013.08.034	journal	December 2013
Mathematical model of immune processes Dibrov, B. F.; Livshits, M. A.; Volkenstein, M. V. Journal of Theoretical Biology, Vol. 65, Issue 4 https://doi.org/10.1016/0022-5193(77)90012-1	journal	April 1977
Exploring the Mechanisms of Primary Antibody Responses to T Cell-Dependent Antigens Oprea, Mihaela; Perelson, Alan S. Journal of Theoretical Biology, Vol. 181, Issue 3 https://doi.org/10.1006/jtbi.1996.0127	journal	August 1996
Diseases of the Liver and Biliary System Sherlock, Sheila; Dooley, James Blackwell Publishing Ltd https://doi.org/10.1002/9780470986820	book	December 2001
Hepatitis B virus clearance rate estimates Dahari, Harel; Cotler, Scott J.; Layden, Thomas J. Hepatology, Vol. 49, Issue 5 https://doi.org/10.1002/hep.22874	journal	February 2009
Serum levels of immunoglobulins (IgG, IgA, IgM) in a general adult population and their relationship with alcohol consumption, smoking and common metabolic abnormalities: Serum immunoglobulin levels in adults Gonzalez-Quintela, A.; Alende, R.; Gude, F. Clinical & Experimental Immunology, Vol. 151, Issue 1 https://doi.org/10.1111/j.1365-2249.2007.03545.x	journal	November 2007
Unbinding forces of single antibody-antigen complexes correlate with their thermal dissociation rates Schwesinger, F.; Ros, R.; Strunz, T. Proceedings of the National Academy of Sciences, Vol. 97, Issue 18 https://doi.org/10.1073/pnas.97.18.9972	journal	August 2000
Early high-affinity neutralizing anti-viral IgG responses without further overall improvements of affinity. Roost, H. P.; Bachmann, M. F.; Haag, A. Proceedings of the National Academy of Sciences, Vol. 92, Issue 5 https://doi.org/10.1073/pnas.92.5.1257	journal	February 1995
Human immunodeficiency virus type 1 neutralizing antibodies accelerate clearance of cell–free virions from blood plasma Igarashi, Tatsuhiko; Brown, Charles; Azadegan, Ali Nature Medicine, Vol. 5, Issue 2 https://doi.org/10.1038/5576	journal	February 1999
Molecular epidemiology of a large outbreak of hepatitis B linked to autohaemotherapy Webster, George JM; Hallett, Rachel; Whalley, Simon A. The Lancet, Vol. 356, Issue 9227 https://doi.org/10.1016/S0140-6736(00)02529-0	journal	July 2000
Kinetics of Acute Hepatitis B Virus Infection in Humans Whalley, Simon A.; Murray, John M.; Brown, Dave The Journal of Experimental Medicine, Vol. 193, Issue 7 https://doi.org/10.1084/jem.193.7.847	journal	April 2001
Occupancy and mechanism in antibody-mediated neutralization of animal viruses Klasse, P. J.; Sattentau, Q. J. Journal of General Virology, Vol. 83, Issue 9 https://doi.org/10.1099/0022-1317-83-9-2091	journal	September 2002
Stoichiometry of Antibody Neutralization of Human Immunodeficiency Virus Type 1 Yang, Xinzhen; Kurteva, Svetla; Lee, Sandra Journal of Virology, Vol. 79, Issue 6 https://doi.org/10.1128/JVI.79.6.3500-3508.2005	journal	March 2005
Restricted occupancy models for neutralization of HIV virions and populations Magnus, Carsten; Regoes, Roland R. Journal of Theoretical Biology, Vol. 283, Issue 1 https://doi.org/10.1016/j.jtbi.2011.06.004	journal	August 2011
Virus Neutralisation: New Insights from Kinetic Neutralisation Curves Magnus, Carsten PLoS Computational Biology, Vol. 9, Issue 2 https://doi.org/10.1371/journal.pcbi.1002900	journal	February 2013
Sensitivity analysis of a nonlinear lumped parameter model of HIV infection dynamics Bortz, D. Bulletin of Mathematical Biology, Vol. 66, Issue 5 https://doi.org/10.1016/j.bulm.2003.10.011	journal	September 2004
Model for competition from self during passive immunization, with application to broadly neutralizing antibodies for HIV Ali Tabei, S. M.; Li, Ying; Weigert, Martin Vaccine, Vol. 30, Issue 3 https://doi.org/10.1016/j.vaccine.2011.11.048	journal	January 2012
Initial B-Cell Responses to Transmitted Human Immunodeficiency Virus Type 1: Virion-Binding Immunoglobulin M (IgM) and IgG Antibodies Followed by Plasma Anti-gp41 Antibodies with Ineffective Control of Initial Viremia Tomaras, G. D.; Yates, N. L.; Liu, P. Journal of Virology, Vol. 82, Issue 24, p. 12449-12463 https://doi.org/10.1128/JVI.01708-08	journal	October 2008
Antibody Levels and Protection after Hepatitis B Vaccination: Results of a 15-Year Follow-up McMahon, Brian J.; Bruden, Dana L.; Petersen, Kenneth M. Annals of Internal Medicine, Vol. 142, Issue 5 https://doi.org/10.7326/0003-4819-142-5-200503010-00008	journal	March 2005
Antibody Levels and Protection after Hepatitis B Vaccine: Results of a 22‐Year Follow‐Up Study and Response to a Booster Dose McMahon, Brian J.; Dentinger, Catherine M.; Bruden, Dana The Journal of Infectious Diseases, Vol. 200, Issue 9 https://doi.org/10.1086/606119	journal	November 2009
Immunoglobulin Concentrations in Sera of Normal Children: Quantitation against an International Reference Preparation Čejka, Jan; Mood, Darlene W.; Su Kim, Chung Clinical Chemistry, Vol. 20, Issue 6 https://doi.org/10.1093/clinchem/20.6.656	journal	June 1974
The global health burden of infection-associated cancers in the year 2002 Parkin, Donald Maxwell International Journal of Cancer, Vol. 118, Issue 12 https://doi.org/10.1002/ijc.21731	journal	January 2006
Recovery efficiencies of nucleic acid extraction kits as measured by quantitative LightCyclerTM PCR Read, S. J. Molecular Pathology, Vol. 54, Issue 2 https://doi.org/10.1136/mp.54.2.86	journal	April 2001
Liver Regeneration Fausto, Nelson; Campbell, Jen S. The Liver: Biology and Pathobiology https://doi.org/10.1002/9780470747919.ch36	book	October 2009
Mathematical model of immune processes Dibrov, B. F.; Livshits, M. A.; Volkenstein, M. V. Journal of Theoretical Biology, Vol. 69, Issue 1 https://doi.org/10.1016/0022-5193(77)90386-1	journal	November 1977
Liver Regeneration Trautwein, Christian Zakim and Boyer's Hepatology https://doi.org/10.1016/b978-1-4160-3258-8.50007-3	book	January 2006
Stoichiometry of Antibody Neutralization of Human Immunodeficiency Virus Type 1 Yang, Xinzhen; Kurteva, Svetla; Lee, Sandra Journal of Virology, Vol. 79, Issue 11 https://doi.org/10.1128/jvi.79.11.7279.2005	journal	June 2005
Diseases of the Liver and Biliary System Sherlock, Shelia Postgraduate Medical Journal, Vol. 45, Issue 522, p. 304-304 https://doi.org/10.1136/pgmj.45.522.304-a	journal	April 1959
Initial B-Cell Responses to Transmitted Human Immunodeficiency Virus Type 1: Virion-Binding Immunoglobulin M (IgM) and IgG Antibodies Followed by Plasma Anti-gp41 Antibodies with Ineffective Control of Initial Viremia F., Keele, Brandon; B., Hicks, Charles; T., Lucas, Judith The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/7sbj-h392	text	January 2008
Virus Neutralisation: New Insights from Kinetic Neutralisation Curves Magnus, Carsten ETH Zurich https://doi.org/10.3929/ethz-b-000104705	text	January 2013
Diseases of the Liver and Biliary System Iber, Frank JAMA: The Journal of the American Medical Association, Vol. 278, Issue 23 https://doi.org/10.1001/jama.1997.03550230092048	journal	December 1997
Liver Regeneration Ray, Debolina; Han, Yuyan; Maroni, Luca Liver Regeneration https://doi.org/10.1016/b978-0-12-420128-6.00016-6	book	January 2015
Initial B-Cell Responses to Transmitted Human Immunodeficiency Virus Type 1: Virion-Binding Immunoglobulin M (IgM) and IgG Antibodies Followed by Plasma Anti-gp41 Antibodies with Ineffective Control of Initial Viremia F., Haynes, B.; T., Lucas, J.; D., Tomaras, G. The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/tbz9-v590	text	January 2008
Liver regeneration de Jonge, Jeroen; Olthoff, Kim M. Blumgart's Surgery of the Liver, Biliary Tract and Pancreas, 2-Volume Set https://doi.org/10.1016/b978-0-323-34062-5.00006-6	book	January 2017
Diseases of the Liver and Biliary System Sorrell, Michael F. Gastroenterology, Vol. 124, Issue 2 https://doi.org/10.1053/gast.2003.1240579a	journal	February 2003
Liver Regeneration Michalopoulos, George K. Molecular Pathology Library https://doi.org/10.1007/978-1-4419-7107-4_18	book	November 2010
Liver Regeneration Michalopoulos, George K. The Liver: Biology and Pathobiology https://doi.org/10.1002/9781119436812.ch45	book	January 2020
Virion half-life in chronic hepatitis B infection is strongly correlated with levels of viremia Dandri, Maura; Murray, John M.; Lutgehetmann, Marc Hepatology, Vol. 48, Issue 4 https://doi.org/10.1002/hep.22469	journal	August 2008
Early intrahepatic CD8 responses in HBV pathogenesis: A new piece of the puzzle Missale, Gabriele Journal of Hepatology, Vol. 45, Issue 2 https://doi.org/10.1016/j.jhep.2006.05.004	journal	August 2006
Kinetic and affinity limits on antibodies produced during immune responses. Foote, J.; Eisen, H. N. Proceedings of the National Academy of Sciences, Vol. 92, Issue 5 https://doi.org/10.1073/pnas.92.5.1254	journal	February 1995
Drastic Reduction in the Production of Subviral Particles Does Not Impair Hepatitis B Virus Virion Secretion Garcia, Tamako; Li, Jisu; Sureau, Camille Journal of Virology, Vol. 83, Issue 21 https://doi.org/10.1128/jvi.00905-09	journal	August 2009
Apoptosis and Regeneration of Hepatocytes during Recovery from Transient Hepadnavirus Infections Guo, Ju-Tao; Zhou, Huan; Liu, Chen Journal of Virology, Vol. 74, Issue 3 https://doi.org/10.1128/jvi.74.3.1495-1505.2000	journal	February 2000
Relative Sensitivity of Hepatitis B Virus and Other Hepatotropic Viruses to the Antiviral Effects of Cytokines McClary, Heike; Koch, Rick; Chisari, Francis V. Journal of Virology, Vol. 74, Issue 5 https://doi.org/10.1128/jvi.74.5.2255-2264.2000	journal	March 2000
Intrahepatic Induction of Alpha/Beta Interferon Eliminates Viral RNA-Containing Capsids in Hepatitis B Virus Transgenic Mice Wieland, Stefan F.; Guidotti, Luca G.; Chisari, Francis V. Journal of Virology, Vol. 74, Issue 9 https://doi.org/10.1128/jvi.74.9.4165-4173.2000	journal	May 2000
Control of rate and extent of the proliferative response after partial hepatectomy Lambotte, Luc; Saliez, Alain; Triest, Sandrine American Journal of Physiology-Gastrointestinal and Liver Physiology, Vol. 273, Issue 4 https://doi.org/10.1152/ajpgi.1997.273.4.g905	journal	October 1997
Metabolic properties of IgG subclasses in man Morell, Andreas; Terry, William D.; Waldmann, Thomas A. Journal of Clinical Investigation, Vol. 49, Issue 4 https://doi.org/10.1172/jci106279	journal	April 1970

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