This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nam, J.-H. Articles by Bukh, J. Search for Related Content PubMed PubMed Citation Articles by Nam, J.-H. Articles by Bukh, J.

 Previous Article  |  Next Article 

Journal of Virology, September 2004, p. 9389-9399, Vol. 78, No. 17
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.17.9389-9399.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

In Vivo Analysis of the 3' Untranslated Region of GB Virus B after In Vitro Mutagenesis of an Infectious cDNA Clone: Persistent Infection in a Transfected Tamarin

Jae-Hwan Nam,^1, Kristina Faulk,¹ Ronald E. Engle,¹ Sugantha Govindarajan,² Marisa St. Claire,³ and Jens Bukh^1*

Hepatitis Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda,¹ BIOQUAL, Inc., Rockville, Maryland,³ Liver Research Laboratory, Rancho Los Amigos Medical Center, Downey, California²

Received 4 March 2004/ Accepted 22 April 2004

GB virus B (GBV-B), the virus most closely related to hepatitis C virus (HCV), infects tamarins and causes acute hepatitis. The 3' untranslated region (UTR) of an infectious GBV-B clone (pGBB) has a proximal short sequence followed by a poly(U) tract and a 3' terminal sequence. Our investigators previously demonstrated that the 3' terminal sequence was critical for in vivo infectivity. Here, we tested the effect of deleting the short sequence and/or the poly(U) tract from pGBB; infectivity of each mutant was tested by intrahepatic transfection of two tamarins with transcribed RNA. A mutant lacking both regions was not viable. However, mutants lacking either the short sequence or the poly(U) tract were viable. All four tamarins had a wild-type-like acute infection and developed acute hepatitis. Whereas we found that five tamarins transfected with the wild-type clone pGBB had acute resolving infection, one tamarin transfected with the poly(U) deletion mutant became persistently infected. This animal had viremia and hepatitis until its death at week 90. The genomes recovered at weeks 2, 7, 15, 20, 60, and 90 lacked the poly(U) stretch. Eight amino acid changes were identified at week 90. One change, in the putative p7 protein, was dominant at week 15. Thus, persistence of GBV-B, like persistence of HCV, was associated with the emergence of virus variants. Four tamarins inoculated with serum collected at weeks 2 and 90 from the tamarin with persistent infection had an acute resolving infection. Nonetheless, the demonstration that GBV-B can persist in tamarins strengthens its relevance as a surrogate model for the study of HCV.

Present address: Department of Biomedical Science, Korea National Institute of Health, Eunpyung-gu, Seoul, Korea 122-701.

This article has been cited by other articles:

• Mankouri, J., Milward, A., Pryde, K. R., Warter, L., Martin, A., Harris, M. (2008). A comparative cell biological analysis reveals only limited functional homology between the NS5A proteins of hepatitis C virus and GB virus B. J. Gen. Virol. 89: 1911-1920 [Abstract] [Full Text]  
• Haqshenas, G., Dong, X., Netter, H., Torresi, J., Gowans, E. J. (2007). A chimeric GB virus B encoding the hepatitis C virus hypervariable region 1 is infectious in vivo. J. Gen. Virol. 88: 895-902 [Abstract] [Full Text]  
• Chen, Z., Benureau, Y., Rijnbrand, R., Yi, J., Wang, T., Warter, L., Lanford, R. E., Weinman, S. A., Lemon, S. M., Martin, A., Li, K. (2007). GB Virus B Disrupts RIG-I Signaling by NS3/4A-Mediated Cleavage of the Adaptor Protein MAVS. J. Virol. 81: 964-976 [Abstract] [Full Text]  
• Targett-Adams, P., Schaller, T., Hope, G., Lanford, R. E., Lemon, S. M., Martin, A., McLauchlan, J. (2006). Signal Peptide Peptidase Cleavage of GB Virus B Core Protein Is Required for Productive Infection in Vivo. J. Biol. Chem. 281: 29221-29227 [Abstract] [Full Text]  
• Takikawa, S., Engle, R. E., Emerson, S. U., Purcell, R. H., St. Claire, M., Bukh, J. (2006). Functional analyses of GB virus B p13 protein: Development of a recombinant GB virus B hepatitis virus with a p7 protein. Proc. Natl. Acad. Sci. USA 103: 3345-3350 [Abstract] [Full Text]