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Journal of Virology, October 2002, p. 10465-10472, Vol. 76, No. 20
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.20.10465-10472.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

A Prenylation Inhibitor Prevents Production of Infectious Hepatitis Delta Virus Particles

Bruno B. Bordier,1,2 Patricia L. Marion,1 Kazuo Ohashi,3 Mark A. Kay,3 Harry B. Greenberg,1,2,4,{dagger} John L. Casey,5 and Jeffrey S. Glenn1,2*

Division of Gastroenterology and Hepatology,1 Department of Microbiology and Immunology,4 Program in Human Gene Therapy, Departments of Pediatrics and Genetics, Stanford University School of Medicine,3 Veterans Administration Medical Center, Palo Alto, California,2 Division of Molecular Virology and Immunology, Georgetown University Medical Center, Rockville, Maryland5

Received 14 February 2002/ Accepted 2 July 2002

Hepatitis delta virus (HDV) causes both acute and chronic liver disease throughout the world. Effective medical therapy is lacking. Previous work has shown that the assembly of HDV virus-like particles (VLPs) could be abolished by BZA-5B, a compound with farnesyltransferase inhibitory activity. Here we show that FTI-277, another farnesyltransferase inhibitor, prevented the production of complete, infectious HDV virions of two different genotypes. Thus, in spite of the added complexity and assembly determinants of infectious HDV virions compared to VLPs, the former are also sensitive to pharmacological prenylation inhibition. Moreover, production of HDV genotype III virions, which is associated with particularly severe clinical disease, was as sensitive to prenylation inhibition as was that of HDV genotype I virions. Farnesyltransferase inhibitors thus represent an attractive potential class of novel antiviral agents for use against HDV, including the genotypes associated with most severe disease.

* Corresponding author. Mailing addressed: Division of Gastroenterology and Hepatology, Stanford University School of Medicine, CCSR Building, Room 3115, 269 Campus Dr., Palo Alto, CA 94305-5187. Phone: (650) 725-3373. Fax: (650) 723-5488. E-mail: jeffrey.glenn{at}stanford.edu.

{dagger} Present address: Medimmune, Inc., Mountain View, CA 94043.

Journal of Virology, October 2002, p. 10465-10472, Vol. 76, No. 20
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.20.10465-10472.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Gudima, S., He, Y., Chai, N., Bruss, V., Urban, S., Mason, W., Taylor, J. (2008). Primary Human Hepatocytes Are Susceptible to Infection by Hepatitis Delta Virus Assembled with Envelope Proteins of Woodchuck Hepatitis Virus. J. Virol. 82: 7276-7283 [Abstract] [Full Text]  
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  • O'Malley, B., Lazinski, D. W. (2005). Roles of Carboxyl-Terminal and Farnesylated Residues in the Functions of the Large Hepatitis Delta Antigen. J. Virol. 79: 1142-1153 [Abstract] [Full Text]  
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  • Einav, S., Glenn, J. S. (2003). Prenylation inhibitors: a novel class of antiviral agents. J Antimicrob Chemother 52: 883-886 [Abstract] [Full Text]  


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