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Hepatitis C virus epitope-specific neutralizing antibodies in Igs prepared from human plasma

Neutralizing antibodies directed against hepatitis C virus (HCV) are present in Igs made from anti-HCV-positive plasma. However, these HCV-specific Igs are largely ineffective in vivo. The mechanism for the poor effectiveness is currently unknown. We hypothesize that the presence of nonneutralizing...

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Autores principales: Zhang, Pei, Wu, Charles G., Mihalik, Kathleen, Virata, Maria Luisa, Yu, Mei-ying W., Alter, Harvey J., Feinstone, Stephen M.
Formato: Texto
Lenguaje:English
Publicado: National Academy of Sciences 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1866310/
https://www.ncbi.nlm.nih.gov/pubmed/17494735
http://dx.doi.org/10.1073/pnas.0703039104
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author Zhang, Pei
Wu, Charles G.
Mihalik, Kathleen
Virata, Maria Luisa
Yu, Mei-ying W.
Alter, Harvey J.
Feinstone, Stephen M.
author_facet Zhang, Pei
Wu, Charles G.
Mihalik, Kathleen
Virata, Maria Luisa
Yu, Mei-ying W.
Alter, Harvey J.
Feinstone, Stephen M.
author_sort Zhang, Pei
collection PubMed
description Neutralizing antibodies directed against hepatitis C virus (HCV) are present in Igs made from anti-HCV-positive plasma. However, these HCV-specific Igs are largely ineffective in vivo. The mechanism for the poor effectiveness is currently unknown. We hypothesize that the presence of nonneutralizing antibodies in HCV-specific Igs interferes with the function of neutralizing antibodies, resulting in the reduction or blockage of their effect. In the present study, we identified at least two epitopes at amino acid residues 412–419 (epitope I) and 434–446 (epitope II), located downstream of the hypervariable region I within the HCV E2 protein. We demonstrated that epitope I, but not epitope II, was implicated in HCV neutralization and that binding of a nonneutralizing antibody to epitope II completely disrupted virus neutralization mediated by antibody binding at epitope I. The dynamic interaction between nonneutralizing and neutralizing antibodies may thus play a key role in determining the outcomes of HCV infection. Further exploration of this interplay should lead to a better understanding of the mechanisms of neutralization and immune escape and may indicate pathways for the manufacture of an effective HCV-specific Ig product for immune prophylaxis of HCV infection.
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spelling pubmed-18663102007-06-27 Hepatitis C virus epitope-specific neutralizing antibodies in Igs prepared from human plasma Zhang, Pei Wu, Charles G. Mihalik, Kathleen Virata, Maria Luisa Yu, Mei-ying W. Alter, Harvey J. Feinstone, Stephen M. Proc Natl Acad Sci U S A Biological Sciences Neutralizing antibodies directed against hepatitis C virus (HCV) are present in Igs made from anti-HCV-positive plasma. However, these HCV-specific Igs are largely ineffective in vivo. The mechanism for the poor effectiveness is currently unknown. We hypothesize that the presence of nonneutralizing antibodies in HCV-specific Igs interferes with the function of neutralizing antibodies, resulting in the reduction or blockage of their effect. In the present study, we identified at least two epitopes at amino acid residues 412–419 (epitope I) and 434–446 (epitope II), located downstream of the hypervariable region I within the HCV E2 protein. We demonstrated that epitope I, but not epitope II, was implicated in HCV neutralization and that binding of a nonneutralizing antibody to epitope II completely disrupted virus neutralization mediated by antibody binding at epitope I. The dynamic interaction between nonneutralizing and neutralizing antibodies may thus play a key role in determining the outcomes of HCV infection. Further exploration of this interplay should lead to a better understanding of the mechanisms of neutralization and immune escape and may indicate pathways for the manufacture of an effective HCV-specific Ig product for immune prophylaxis of HCV infection. National Academy of Sciences 2007-05-15 /pmc/articles/PMC1866310/ /pubmed/17494735 http://dx.doi.org/10.1073/pnas.0703039104 Text en Freely available online through the PNAS open access option.
spellingShingle Biological Sciences
Zhang, Pei
Wu, Charles G.
Mihalik, Kathleen
Virata, Maria Luisa
Yu, Mei-ying W.
Alter, Harvey J.
Feinstone, Stephen M.
Hepatitis C virus epitope-specific neutralizing antibodies in Igs prepared from human plasma
title Hepatitis C virus epitope-specific neutralizing antibodies in Igs prepared from human plasma
title_full Hepatitis C virus epitope-specific neutralizing antibodies in Igs prepared from human plasma
title_fullStr Hepatitis C virus epitope-specific neutralizing antibodies in Igs prepared from human plasma
title_full_unstemmed Hepatitis C virus epitope-specific neutralizing antibodies in Igs prepared from human plasma
title_short Hepatitis C virus epitope-specific neutralizing antibodies in Igs prepared from human plasma
title_sort hepatitis c virus epitope-specific neutralizing antibodies in igs prepared from human plasma
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1866310/
https://www.ncbi.nlm.nih.gov/pubmed/17494735
http://dx.doi.org/10.1073/pnas.0703039104
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