In vivo antiviral efficacy of prenylation inhibitors against hepatitis delta virus

Bruno B. Bordier, Junko Ohkanda, Ping Liu, So Young Lee, F. H. Salazar, Patricia L. Marion, Kazuo Ohashi, Leonard Meuse, Mark A. Kay, John L. Casey, Saïd M. Sebti, Andrew Hamilton, Jeffrey S. Glenn

Research output: Contribution to journalArticle

Abstract

Hepatitis delta virus (HDV) can dramatically worsen liver disease in patients coinfected with hepatitis B virus (HBV). No effective medical therapy exists for HDV. The HDV envelope requires HBV surface antigen proteins provided by HBV. Once inside a cell, however, HDV can replicate its genome in the absence of any HBV gene products. In vitro, HDV virion assembly is critically dependent on prenyl lipid modification, or prenylation, of its nucleocapsid-like protein large delta antigen. To overcome limitations of current animal models and to test the hypothesis that pharmacologic prenylation inhibition can prevent the production of HDV virions in vivo, we established a convenient mouse-based model of HDV infection capable of yielding viremia. Such mice were then treated with the prenylation inhibitors FTI-277 and FTI-2153. Both agents were highly effective at clearing HDV viremia. As expected, HDV inhibition exhibited duration-of-treatment dependence. These results provide the first preclinical data supporting the in vivo efficacy of prenylation inhibition as a novel antiviral therapy with potential application to HDV and a wide variety of other viruses.

Original languageEnglish (US)
Pages (from-to)407-414
Number of pages8
JournalJournal of Clinical Investigation
Volume112
Issue number3
DOIs
StatePublished - Aug 2003

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Hepatitis Delta Virus
Prenylation
Antiviral Agents
Hepatitis B virus
Viremia
Virion
Hepatitis delta Antigens
Hepatitis D
Nucleocapsid Proteins
Virus Assembly
Virus Diseases
Hepatitis B Surface Antigens
Liver Diseases
Membrane Proteins
Therapeutics
Animal Models
Genome

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Bordier, B. B., Ohkanda, J., Liu, P., Lee, S. Y., Salazar, F. H., Marion, P. L., ... Glenn, J. S. (2003). In vivo antiviral efficacy of prenylation inhibitors against hepatitis delta virus. Journal of Clinical Investigation, 112(3), 407-414. https://doi.org/10.1172/JCI200317704

In vivo antiviral efficacy of prenylation inhibitors against hepatitis delta virus. / Bordier, Bruno B.; Ohkanda, Junko; Liu, Ping; Lee, So Young; Salazar, F. H.; Marion, Patricia L.; Ohashi, Kazuo; Meuse, Leonard; Kay, Mark A.; Casey, John L.; Sebti, Saïd M.; Hamilton, Andrew; Glenn, Jeffrey S.

In: Journal of Clinical Investigation, Vol. 112, No. 3, 08.2003, p. 407-414.

Research output: Contribution to journalArticle

Bordier, BB, Ohkanda, J, Liu, P, Lee, SY, Salazar, FH, Marion, PL, Ohashi, K, Meuse, L, Kay, MA, Casey, JL, Sebti, SM, Hamilton, A & Glenn, JS 2003, 'In vivo antiviral efficacy of prenylation inhibitors against hepatitis delta virus', Journal of Clinical Investigation, vol. 112, no. 3, pp. 407-414. https://doi.org/10.1172/JCI200317704
Bordier, Bruno B. ; Ohkanda, Junko ; Liu, Ping ; Lee, So Young ; Salazar, F. H. ; Marion, Patricia L. ; Ohashi, Kazuo ; Meuse, Leonard ; Kay, Mark A. ; Casey, John L. ; Sebti, Saïd M. ; Hamilton, Andrew ; Glenn, Jeffrey S. / In vivo antiviral efficacy of prenylation inhibitors against hepatitis delta virus. In: Journal of Clinical Investigation. 2003 ; Vol. 112, No. 3. pp. 407-414.
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