Chimeric GB virus B genomes containing hepatitis C virus p7 are infectious in vivo.
OBJECTIVE
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.
Institute of Molecular and Cellular Biology, Faculty of Biological Sciences and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK. s.d.c.griffin@leeds.ac.uk
Stephen
S
Griffin
Rachel
R
Trowbridge
Pia
P
Thommes
Nigel
N
Parry
David
D
Rowlands
Mark
M
Harris
Helen
H
Bright
D000547:Amantadine / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D002144:Callithrix; D002460:Cell Line; D004195:Disease Models, Animal; D015195:Drug Design; D029406:GB virus B / Q000235:genetics*; D016679:Genome, Viral; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000821:virology*; D022781:Hepatocytes / Q000166:cytology / Q000821:virology; D006801:Humans; D007668:Kidney / Q000166:cytology; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics*; D014162:Transfection; D014764:Viral Proteins / Q000235:genetics*; D000086082:Viroporin Proteins
D000547:Amantadine; D000998:Antiviral Agents; D012367:RNA, Viral; D011993:Recombinant Fusion Proteins; D014764:Viral Proteins; C088369:p7 protein, Hepatitis C virus; D000086082:Viroporin Proteins