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Chimeric GB virus B genomes containing hepatitis C virus p7 are infectious in vivo()

BACKGROUND/AIMS: The development of new therapies for hepatitis C virus (HCV) infection has been hampered by the lack of a small animal model. GB virus B (GBV-B), which infects new world monkeys, has been proposed as a surrogate system for HCV replication. Despite their short genetic distance, howev...

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Autores principales: Griffin, Stephen, Trowbridge, Rachel, Thommes, Pia, Parry, Nigel, Rowlands, David, Harris, Mark, Bright, Helen
Formato: Texto
Lenguaje:English
Publicado: Elsevier 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3098382/
https://www.ncbi.nlm.nih.gov/pubmed/18845353
http://dx.doi.org/10.1016/j.jhep.2008.07.020
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author Griffin, Stephen
Trowbridge, Rachel
Thommes, Pia
Parry, Nigel
Rowlands, David
Harris, Mark
Bright, Helen
author_facet Griffin, Stephen
Trowbridge, Rachel
Thommes, Pia
Parry, Nigel
Rowlands, David
Harris, Mark
Bright, Helen
author_sort Griffin, Stephen
collection PubMed
description BACKGROUND/AIMS: The development of new therapies for hepatitis C virus (HCV) infection has been hampered by the lack of a small animal model. GB virus B (GBV-B), which infects new world monkeys, has been proposed as a surrogate system for HCV replication. Despite their short genetic distance, however, difficulties exist when extrapolating results from GBV-B to the HCV system. One way of addressing this is the creation of chimeric GBV-B containing HCV elements. METHODS: Construction and analysis of GBV-B chimeras in which the p13 ion channel was replaced by its HCV counterpart, p7. RESULTS: Replacing all, or part of, the GBV-B p13 protein with HCV p7 resulted in viable chimeras which replicated at wild-type levels in marmosets following intra-hepatic RNA injection. Serum from one animal injected with chimeric RNA was infectious in three naïve recipients, indicating that chimeras formed fully infectious virions. Amantadine, which blocks the ion channel activity of both HCV and GBV-B proteins in vitro, also inhibited GBV-B replication in primary hepatocytes. CONCLUSIONS: These viruses highlight the potential for chimeric GBV-B in the development of HCV-specific therapies and will provide a means of developing HCV p7 as a therapeutic target.
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spelling pubmed-30983822011-07-13 Chimeric GB virus B genomes containing hepatitis C virus p7 are infectious in vivo() Griffin, Stephen Trowbridge, Rachel Thommes, Pia Parry, Nigel Rowlands, David Harris, Mark Bright, Helen J Hepatol Article BACKGROUND/AIMS: The development of new therapies for hepatitis C virus (HCV) infection has been hampered by the lack of a small animal model. GB virus B (GBV-B), which infects new world monkeys, has been proposed as a surrogate system for HCV replication. Despite their short genetic distance, however, difficulties exist when extrapolating results from GBV-B to the HCV system. One way of addressing this is the creation of chimeric GBV-B containing HCV elements. METHODS: Construction and analysis of GBV-B chimeras in which the p13 ion channel was replaced by its HCV counterpart, p7. RESULTS: Replacing all, or part of, the GBV-B p13 protein with HCV p7 resulted in viable chimeras which replicated at wild-type levels in marmosets following intra-hepatic RNA injection. Serum from one animal injected with chimeric RNA was infectious in three naïve recipients, indicating that chimeras formed fully infectious virions. Amantadine, which blocks the ion channel activity of both HCV and GBV-B proteins in vitro, also inhibited GBV-B replication in primary hepatocytes. CONCLUSIONS: These viruses highlight the potential for chimeric GBV-B in the development of HCV-specific therapies and will provide a means of developing HCV p7 as a therapeutic target. Elsevier 2008-12 /pmc/articles/PMC3098382/ /pubmed/18845353 http://dx.doi.org/10.1016/j.jhep.2008.07.020 Text en © 2008 Elsevier B.V. https://creativecommons.org/licenses/by/4.0/ Open Access under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/) license
spellingShingle Article
Griffin, Stephen
Trowbridge, Rachel
Thommes, Pia
Parry, Nigel
Rowlands, David
Harris, Mark
Bright, Helen
Chimeric GB virus B genomes containing hepatitis C virus p7 are infectious in vivo()
title Chimeric GB virus B genomes containing hepatitis C virus p7 are infectious in vivo()
title_full Chimeric GB virus B genomes containing hepatitis C virus p7 are infectious in vivo()
title_fullStr Chimeric GB virus B genomes containing hepatitis C virus p7 are infectious in vivo()
title_full_unstemmed Chimeric GB virus B genomes containing hepatitis C virus p7 are infectious in vivo()
title_short Chimeric GB virus B genomes containing hepatitis C virus p7 are infectious in vivo()
title_sort chimeric gb virus b genomes containing hepatitis c virus p7 are infectious in vivo()
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3098382/
https://www.ncbi.nlm.nih.gov/pubmed/18845353
http://dx.doi.org/10.1016/j.jhep.2008.07.020
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