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Characterization of the Specific CD4(+) T Cell Response against the F Protein during Chronic Hepatitis C Virus Infection

BACKGROUND: The hepatitis C virus (HCV) Alternate Reading Frame Protein (ARFP or F protein) presents a double-frame shift product of the HCV core gene. We and others have previously reported that the specific antibodies against the F protein could be raised in the sera of HCV chronically infected pa...

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Autores principales: Gao, De-Yong, Jin, Gen-Di, Yao, Bi-Lian, Zhang, Dong-Hua, Gu, Lei-Lei, Lu, Zhi-Meng, Gong, Qiming, Lone, Yu-Chun, Deng, Qiang, Zhang, Xin-Xin
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2997803/
https://www.ncbi.nlm.nih.gov/pubmed/21151917
http://dx.doi.org/10.1371/journal.pone.0014237
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author Gao, De-Yong
Jin, Gen-Di
Yao, Bi-Lian
Zhang, Dong-Hua
Gu, Lei-Lei
Lu, Zhi-Meng
Gong, Qiming
Lone, Yu-Chun
Deng, Qiang
Zhang, Xin-Xin
author_facet Gao, De-Yong
Jin, Gen-Di
Yao, Bi-Lian
Zhang, Dong-Hua
Gu, Lei-Lei
Lu, Zhi-Meng
Gong, Qiming
Lone, Yu-Chun
Deng, Qiang
Zhang, Xin-Xin
author_sort Gao, De-Yong
collection PubMed
description BACKGROUND: The hepatitis C virus (HCV) Alternate Reading Frame Protein (ARFP or F protein) presents a double-frame shift product of the HCV core gene. We and others have previously reported that the specific antibodies against the F protein could be raised in the sera of HCV chronically infected patients. However, the specific CD4(+) T cell responses against the F protein during HCV infection and the pathological implications remained unclear. In the current study, we screened the MHC class II-presenting epitopes of the F protein through HLA-transgenic mouse models and eventually validated the specific CD4(+) T cell responses in HCV chronically infected patients. METHODOLOGY: DNA vaccination in HLA-DR1 and-DP4 transgenic mouse models, proliferation assay to test the F protein specific T cell response, genotyping of Chronic HCV patients and testing the F-peptide stimulated T cell response in the peripheral blood mononuclear cell (PBMC) by in vitro expansion and interferon (IFN)- γ intracellular staining. PRINCIPAL FINDINGS: At least three peptides within HCV F protein were identified as HLA-DR or HLA-DP4 presenting epitopes by the proliferation assays in mouse models. Further study with human PBMCs evidenced the specific CD4(+) T cell responses against HCV F protein as well in patients chronically infected with HCV. CONCLUSION: The current study provided the evidence for the first time that HCV F protein could elicit specific CD4(+) T cell response, which may provide an insight into the immunopathogenesis during HCV chronic infection.
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spelling pubmed-29978032010-12-10 Characterization of the Specific CD4(+) T Cell Response against the F Protein during Chronic Hepatitis C Virus Infection Gao, De-Yong Jin, Gen-Di Yao, Bi-Lian Zhang, Dong-Hua Gu, Lei-Lei Lu, Zhi-Meng Gong, Qiming Lone, Yu-Chun Deng, Qiang Zhang, Xin-Xin PLoS One Research Article BACKGROUND: The hepatitis C virus (HCV) Alternate Reading Frame Protein (ARFP or F protein) presents a double-frame shift product of the HCV core gene. We and others have previously reported that the specific antibodies against the F protein could be raised in the sera of HCV chronically infected patients. However, the specific CD4(+) T cell responses against the F protein during HCV infection and the pathological implications remained unclear. In the current study, we screened the MHC class II-presenting epitopes of the F protein through HLA-transgenic mouse models and eventually validated the specific CD4(+) T cell responses in HCV chronically infected patients. METHODOLOGY: DNA vaccination in HLA-DR1 and-DP4 transgenic mouse models, proliferation assay to test the F protein specific T cell response, genotyping of Chronic HCV patients and testing the F-peptide stimulated T cell response in the peripheral blood mononuclear cell (PBMC) by in vitro expansion and interferon (IFN)- γ intracellular staining. PRINCIPAL FINDINGS: At least three peptides within HCV F protein were identified as HLA-DR or HLA-DP4 presenting epitopes by the proliferation assays in mouse models. Further study with human PBMCs evidenced the specific CD4(+) T cell responses against HCV F protein as well in patients chronically infected with HCV. CONCLUSION: The current study provided the evidence for the first time that HCV F protein could elicit specific CD4(+) T cell response, which may provide an insight into the immunopathogenesis during HCV chronic infection. Public Library of Science 2010-12-06 /pmc/articles/PMC2997803/ /pubmed/21151917 http://dx.doi.org/10.1371/journal.pone.0014237 Text en Gao et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Gao, De-Yong
Jin, Gen-Di
Yao, Bi-Lian
Zhang, Dong-Hua
Gu, Lei-Lei
Lu, Zhi-Meng
Gong, Qiming
Lone, Yu-Chun
Deng, Qiang
Zhang, Xin-Xin
Characterization of the Specific CD4(+) T Cell Response against the F Protein during Chronic Hepatitis C Virus Infection
title Characterization of the Specific CD4(+) T Cell Response against the F Protein during Chronic Hepatitis C Virus Infection
title_full Characterization of the Specific CD4(+) T Cell Response against the F Protein during Chronic Hepatitis C Virus Infection
title_fullStr Characterization of the Specific CD4(+) T Cell Response against the F Protein during Chronic Hepatitis C Virus Infection
title_full_unstemmed Characterization of the Specific CD4(+) T Cell Response against the F Protein during Chronic Hepatitis C Virus Infection
title_short Characterization of the Specific CD4(+) T Cell Response against the F Protein during Chronic Hepatitis C Virus Infection
title_sort characterization of the specific cd4(+) t cell response against the f protein during chronic hepatitis c virus infection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2997803/
https://www.ncbi.nlm.nih.gov/pubmed/21151917
http://dx.doi.org/10.1371/journal.pone.0014237
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