The Impact of Hepatitis B Virus Precore/Core Gene Carboxyl Terminal Mutations on Viral Biosynthesis and the Host Immune Response
Background. We aimed to elucidate the impact of hepatitis B virus (HBV) precore/core gene mutations on spontaneous hepatitis Be antigen (HBeAg) seroconversion, HBV biosynthesis, and the human immune responses in chronic HBV–infected patients. Methods. We analyzed the HBV precore/core gene sequences...
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Published in | The Journal of infectious diseases Vol. 209; no. 9; pp. 1374 - 1381 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
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Oxford
Oxford University Press
01.05.2014
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Abstract | Background. We aimed to elucidate the impact of hepatitis B virus (HBV) precore/core gene mutations on spontaneous hepatitis Be antigen (HBeAg) seroconversion, HBV biosynthesis, and the human immune responses in chronic HBV–infected patients. Methods. We analyzed the HBV precore/core gene sequences by cloning method in 33 chronic HBV–infected patients during the inflammatory phase before spontaneous HBeAg seroconversion. The impact of the most prevalent mutant on HBeAg biosynthesis was assessed by Western blotting and native agarose gel analysis in Huh7 cells, and the human immune responses were assessed by in vitro stimulation of CD3⁺ CD8⁺ T lymphocytes of chronic HBV–infected subjects. Results. The P135Q and G1896A were the most prevalent mutants before HBeAg seroconversion, acting as markers of HBeAg seroconversion (hazard ratios = 2.75 and 4.50; P=.01 and <.001, respectively). The P135Q mutants displayed decreased HBeAg secretion and HBV capsid molecular weight, while showing increased 22 kD HBeAg proprotein accumulation in Huh7 cells. The P135Q mutant peptide induced less interferon-γ expression in CD3⁺ CD8⁺ T lymphocytes in HBeAg-negative subjects compared to the wild-type peptide (P = .03). Conclusions. The HBV P135Q mutant emergence during the inflammatory phase was associated with HBeAg seroconversion. It was associated with altered HBV capsid assembly, HBeAg biosynthesis, and reduced human immune responses following HBeAg seroconversion. |
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AbstractList | Background.
We aimed to elucidate the impact of hepatitis B virus (HBV) precore/core gene mutations on spontaneous hepatitis B e antigen (HBeAg) seroconversion, HBV biosynthesis, and the human immune responses in chronic HBV–infected patients.
Methods.
We analyzed the HBV precore/core gene sequences by cloning method in 33 chronic HBV–infected patients during the inflammatory phase before spontaneous HBeAg seroconversion. The impact of the most prevalent mutant on HBeAg biosynthesis was assessed by Western blotting and native agarose gel analysis in Huh7 cells, and the human immune responses were assessed by in vitro stimulation of CD3+CD8+ T lymphocytes of chronic HBV–infected subjects.
Results.
The P135Q and G1896A were the most prevalent mutants before HBeAg seroconversion, acting as markers of HBeAg seroconversion (hazard ratios = 2.75 and 4.50; P = .01 and <.001, respectively). The P135Q mutants displayed decreased HBeAg secretion and HBV capsid molecular weight, while showing increased 22 kD HBeAg proprotein accumulation in Huh7 cells. The P135Q mutant peptide induced less interferon-γ expression in CD3+CD8+ T lymphocytes in HBeAg-negative subjects compared to the wild-type peptide (P = .03).
Conclusions.
The HBV P135Q mutant emergence during the inflammatory phase was associated with HBeAg seroconversion. It was associated with altered HBV capsid assembly, HBeAg biosynthesis, and reduced human immune responses following HBeAg seroconversion. We aimed to elucidate the impact of hepatitis B virus (HBV) precore/core gene mutations on spontaneous hepatitis B e antigen (HBeAg) seroconversion, HBV biosynthesis, and the human immune responses in chronic HBV-infected patients.BACKGROUND We aimed to elucidate the impact of hepatitis B virus (HBV) precore/core gene mutations on spontaneous hepatitis B e antigen (HBeAg) seroconversion, HBV biosynthesis, and the human immune responses in chronic HBV-infected patients. We analyzed the HBV precore/core gene sequences by cloning method in 33 chronic HBV-infected patients during the inflammatory phase before spontaneous HBeAg seroconversion. The impact of the most prevalent mutant on HBeAg biosynthesis was assessed by Western blotting and native agarose gel analysis in Huh7 cells, and the human immune responses were assessed by in vitro stimulation of CD3+ CD8+ T lymphocytes of chronic HBV-infected subjects.METHODS We analyzed the HBV precore/core gene sequences by cloning method in 33 chronic HBV-infected patients during the inflammatory phase before spontaneous HBeAg seroconversion. The impact of the most prevalent mutant on HBeAg biosynthesis was assessed by Western blotting and native agarose gel analysis in Huh7 cells, and the human immune responses were assessed by in vitro stimulation of CD3+ CD8+ T lymphocytes of chronic HBV-infected subjects. The P135Q and G1896A were the most prevalent mutants before HBeAg seroconversion, acting as markers of HBeAg seroconversion (hazard ratios = 2.75 and 4.50; P = .01 and <.001, respectively). The P135Q mutants displayed decreased HBeAg secretion and HBV capsid molecular weight, while showing increased 22 kD HBeAg proprotein accumulation in Huh7 cells. The P135Q mutant peptide induced less interferon-γ expression in CD3+ CD8+ T lymphocytes in HBeAg-negative subjects compared to the wild-type peptide (P = .03).RESULTS The P135Q and G1896A were the most prevalent mutants before HBeAg seroconversion, acting as markers of HBeAg seroconversion (hazard ratios = 2.75 and 4.50; P = .01 and <.001, respectively). The P135Q mutants displayed decreased HBeAg secretion and HBV capsid molecular weight, while showing increased 22 kD HBeAg proprotein accumulation in Huh7 cells. The P135Q mutant peptide induced less interferon-γ expression in CD3+ CD8+ T lymphocytes in HBeAg-negative subjects compared to the wild-type peptide (P = .03). The HBV P135Q mutant emergence during the inflammatory phase was associated with HBeAg seroconversion. It was associated with altered HBV capsid assembly, HBeAg biosynthesis, and reduced human immune responses following HBeAg seroconversion.CONCLUSIONS The HBV P135Q mutant emergence during the inflammatory phase was associated with HBeAg seroconversion. It was associated with altered HBV capsid assembly, HBeAg biosynthesis, and reduced human immune responses following HBeAg seroconversion. Background. We aimed to elucidate the impact of hepatitis B virus (HBV) precore/core gene mutations on spontaneous hepatitis Be antigen (HBeAg) seroconversion, HBV biosynthesis, and the human immune responses in chronic HBV–infected patients. Methods. We analyzed the HBV precore/core gene sequences by cloning method in 33 chronic HBV–infected patients during the inflammatory phase before spontaneous HBeAg seroconversion. The impact of the most prevalent mutant on HBeAg biosynthesis was assessed by Western blotting and native agarose gel analysis in Huh7 cells, and the human immune responses were assessed by in vitro stimulation of CD3⁺ CD8⁺ T lymphocytes of chronic HBV–infected subjects. Results. The P135Q and G1896A were the most prevalent mutants before HBeAg seroconversion, acting as markers of HBeAg seroconversion (hazard ratios = 2.75 and 4.50; P=.01 and <.001, respectively). The P135Q mutants displayed decreased HBeAg secretion and HBV capsid molecular weight, while showing increased 22 kD HBeAg proprotein accumulation in Huh7 cells. The P135Q mutant peptide induced less interferon-γ expression in CD3⁺ CD8⁺ T lymphocytes in HBeAg-negative subjects compared to the wild-type peptide (P = .03). Conclusions. The HBV P135Q mutant emergence during the inflammatory phase was associated with HBeAg seroconversion. It was associated with altered HBV capsid assembly, HBeAg biosynthesis, and reduced human immune responses following HBeAg seroconversion. We aimed to elucidate the impact of hepatitis B virus (HBV) precore/core gene mutations on spontaneous hepatitis B e antigen (HBeAg) seroconversion, HBV biosynthesis, and the human immune responses in chronic HBV-infected patients. We analyzed the HBV precore/core gene sequences by cloning method in 33 chronic HBV-infected patients during the inflammatory phase before spontaneous HBeAg seroconversion. The impact of the most prevalent mutant on HBeAg biosynthesis was assessed by Western blotting and native agarose gel analysis in Huh7 cells, and the human immune responses were assessed by in vitro stimulation of CD3+ CD8+ T lymphocytes of chronic HBV-infected subjects. The P135Q and G1896A were the most prevalent mutants before HBeAg seroconversion, acting as markers of HBeAg seroconversion (hazard ratios = 2.75 and 4.50; P = .01 and <.001, respectively). The P135Q mutants displayed decreased HBeAg secretion and HBV capsid molecular weight, while showing increased 22 kD HBeAg proprotein accumulation in Huh7 cells. The P135Q mutant peptide induced less interferon-γ expression in CD3+ CD8+ T lymphocytes in HBeAg-negative subjects compared to the wild-type peptide (P = .03). The HBV P135Q mutant emergence during the inflammatory phase was associated with HBeAg seroconversion. It was associated with altered HBV capsid assembly, HBeAg biosynthesis, and reduced human immune responses following HBeAg seroconversion. Background. We aimed to elucidate the impact of hepatitis B virus (HBV) precore/core gene mutations on spontaneous hepatitis B e antigen (HBeAg) seroconversion, HBV biosynthesis, and the human immune responses in chronic HBV&-; infected patients. Methods. We analyzed the HBV precore/core gene sequences by cloning method in 33 chronic HBV&-; infected patients during the inflammatory phase before spontaneous HBeAg seroconversion. The impact of the most prevalent mutant on HBeAg biosynthesis was assessed by Western blotting and native agarose gel analysis in Huh7 cells, and the human immune responses were assessed by in vitro stimulation of CD3 super(+)CD8 super(+) T lymphocytes of chronic HBV-infected subjects. Results. The P135Q and G1896A were the most prevalent mutants before HBeAg seroconversion, acting as markers of HBeAg seroconversion (hazard ratios = 2.75 and 4.50; P = .01 and <.001, respectively). The P135Q mutants displayed decreased HBeAg secretion and HBV capsid molecular weight, while showing increased 22 kD HBeAg proprotein accumulation in Huh7 cells. The P135Q mutant peptide induced less interferon- gamma expression in CD3 super(+)CD8 super(+) T lymphocytes in HBeAg-negative subjects compared to the wild-type peptide (P = .03). Conclusions. The HBV P135Q mutant emergence during the inflammatory phase was associated with HBeAg seroconversion. It was associated with altered HBV capsid assembly, HBeAg biosynthesis, and reduced human immune responses following HBeAg seroconversion. |
Author | Chen, Huey-Ling Hsu, Hong-Yuan Chang, Mei-Hwei Wu, Jia-Feng Ni, Yen-Hsuan |
Author_xml | – sequence: 1 givenname: Jia-Feng surname: Wu fullname: Wu, Jia-Feng – sequence: 2 givenname: Yen-Hsuan surname: Ni fullname: Ni, Yen-Hsuan – sequence: 3 givenname: Huey-Ling surname: Chen fullname: Chen, Huey-Ling – sequence: 4 givenname: Hong-Yuan surname: Hsu fullname: Hsu, Hong-Yuan – sequence: 5 givenname: Mei-Hwei surname: Chang fullname: Chang, Mei-Hwei |
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CitedBy_id | crossref_primary_10_1016_j_jcv_2018_10_007 crossref_primary_10_1016_j_antiviral_2015_08_004 crossref_primary_10_3892_br_2017_894 crossref_primary_10_1186_s12929_015_0199_y crossref_primary_10_1002_jmv_24830 crossref_primary_10_1093_infdis_jiaa545 crossref_primary_10_3390_pathogens13080662 crossref_primary_10_3748_wjg_v22_i17_4287 crossref_primary_10_1016_S2222_1808_16_61093_9 crossref_primary_10_1111_jvh_12699 crossref_primary_10_3389_fmicb_2023_1213145 crossref_primary_10_3389_fmicb_2022_1020147 crossref_primary_10_1002_hep_30788 crossref_primary_10_1371_journal_pone_0226922 crossref_primary_10_2147_JHC_S307962 |
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Copyright | Copyright © 2014 Oxford University Press on behalf of the Infectious Diseases Society of America The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com . 2013 2015 INIST-CNRS |
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Keywords | immune escape mutant precore/core gene hepatitis B e antigen seroconversion hepatitis B virus hepatitis B e antigen Virus Infection Immune response Gene Hepadnaviridae Orthohepadnavirus Biosynthesis Mutation Hepatitis B virus |
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Snippet | Background. We aimed to elucidate the impact of hepatitis B virus (HBV) precore/core gene mutations on spontaneous hepatitis Be antigen (HBeAg) seroconversion,... Background. We aimed to elucidate the impact of hepatitis B virus (HBV) precore/core gene mutations on spontaneous hepatitis B e antigen (HBeAg)... We aimed to elucidate the impact of hepatitis B virus (HBV) precore/core gene mutations on spontaneous hepatitis B e antigen (HBeAg) seroconversion, HBV... Background. We aimed to elucidate the impact of hepatitis B virus (HBV) precore/core gene mutations on spontaneous hepatitis B e antigen (HBeAg)... |
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SubjectTerms | Adult Amino acids Biological and medical sciences Capsid Capsid Proteins - immunology Cell Line Female Fundamental and applied biological sciences. Psychology Gene expression Genetic mutation Genotypes Hepatitis antigens Hepatitis B - immunology Hepatitis B - virology Hepatitis B Antibodies - blood Hepatitis B Antibodies - immunology Hepatitis B Core Antigens - genetics Hepatitis B Core Antigens - immunology Hepatitis B e Antigens - immunology Hepatitis B virus Hepatitis B virus - genetics Hepatitis B virus - immunology Host-Pathogen Interactions - immunology Humans Infectious diseases Interferon-gamma - immunology Male Medical sciences Microbiology Miscellaneous Mutation Polymerase chain reaction T lymphocytes Transfection Virology VIRUSES Young Adult |
Title | The Impact of Hepatitis B Virus Precore/Core Gene Carboxyl Terminal Mutations on Viral Biosynthesis and the Host Immune Response |
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