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ANIMAL VIRUSES

Use of a Prenylation Inhibitor as a Novel Antiviral Agent

Jeffrey S. Glenn, James C. Marsters Jr., Harry B. Greenberg
Jeffrey S. Glenn
Division of Gastroenterology, and
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James C. Marsters Jr.
Bioorganic Chemistry, Genentech Inc., South San Francisco, California 94080
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Harry B. Greenberg
Division of Gastroenterology, and
Department of Microbiology and Immunology, Stanford University School of Medicine and Veterans Administration Medical Center, Palo Alto, California 94305-5487, and
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DOI: 10.1128/JVI.72.11.9303-9306.1998
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    Fig. 1.

    LH cells produce HDV-like particles. (A) HDV-like particles (lane 1) were immunoprecipitated from clarified medium supernatants (Sup.) of LH cells with a monoclonal antibody to HBsAg and subjected to immunoblot analysis for the presence of large delta antigen. LH cells remaining on the dish were harvested in cell lysis buffer and an aliquot (lane 2) was included in the immunoblot analysis. (B) Particles (lane 1) were isolated by ultracentrifugation of clarified medium supernatants of LH cells and an aliquot was subjected to immunoblot analysis, along with a sample of LH cell lysate (lane 2). L, large delta antigen. The locations of prestained molecular mass markers are shown at the left (in kilodaltons).

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    Fig. 2.

    BZA-5B inhibits prenylation of large delta antigen. Combined in vitro transcription-translation reactions were performed with rabbit reticulocyte lysates programmed with water (lanes 1) or a plasmid encoding large delta antigen (lanes 2 to 7) in the presence of [5-3H]mevalonate and either water (lanes 2), a carrier (0.5 mM DTT and 0.05% DMSO) (lanes 3), or a carrier with 5, 10, 25, or 50 μM BZA-5B, as indicated. Aliquots (1 μl) were subjected to SDS-PAGE and either fluorography (A) or immunoblot analysis (B). L, large delta antigen.

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    Fig. 3.

    BZA-5B inhibits HDV-like-particle production. Duplicate dishes of LH cells were grown in media containing a carrier (0.5 mM DTT and 0.05% DMSO) alone (lanes 1) or a carrier with either 10, 25, or 50 μM BZA-5B. Clarified medium supernatants were analyzed for the presence of HDV-like particles by quantitative immunoblot analysis (A). The underlying cells were harvested and counted, and the presence of large delta antigen was analyzed by immunoblotting (B). Only one of the duplicate set of blots is shown. (C) HBsAg was quantitated in duplicate aliquots of each medium supernatant sample, and the percentage of control HBsAg per cell (light bars) and of control particles per cell (dark bars), determined from the experiment whose results are shown in panel A, at each concentration of BZA-5B is plotted. Error bars represent the average deviations.

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Use of a Prenylation Inhibitor as a Novel Antiviral Agent
Jeffrey S. Glenn, James C. Marsters Jr., Harry B. Greenberg
Journal of Virology Nov 1998, 72 (11) 9303-9306; DOI: 10.1128/JVI.72.11.9303-9306.1998

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Use of a Prenylation Inhibitor as a Novel Antiviral Agent
Jeffrey S. Glenn, James C. Marsters Jr., Harry B. Greenberg
Journal of Virology Nov 1998, 72 (11) 9303-9306; DOI: 10.1128/JVI.72.11.9303-9306.1998
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KEYWORDS

antiviral agents
Benzodiazepines
hepatitis delta virus
Oligopeptides
Protein Prenylation

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