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

JOURNAL OF HEPATOLOGY

卷:49

Article

Griffin, Stephen¹  Trowbridge, Rachel¹  Thommes, Pia²  Parry, Nigel²  Rowlands, David¹  Harris, Mark¹  Bright, Helen² 

[1] Univ Leeds, Fac Biol Sci, Inst Mol & Cellular Biol, Leeds LS2 9JT, W Yorkshire, England

[2] GSK Med Res Ctr, Dept Virol, Stevenage, Herts, England

关键词: Hepatitis C virus;    GB virus B;    p7;    Amantadine;    p13;    Chimeric virus;   

DOI  :  10.1016/j.jhep.2008.07.020

来源: Elsevier

【 摘 要 】

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 naive 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. (C) 2008 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

【 授权许可】

Free