A prenylation inhibitor prevents production of infectious hepatitis delta virus particles.
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.
Bordier
Bruno B
BB
Division of Gastroenterology and Hepatology, Stanford University School of Medicine, 269 Campus Drive, Palo Alto, CA 94305-5187, USA.
Marion
Patricia L
PL
Ohashi
Kazuo
K
Kay
Mark A
MA
Greenberg
Harry B
HB
Casey
John L
JL
Glenn
Jeffrey S
JS
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D051231:Farnesyltranstransferase; D003698:Hepatitis Delta Virus / Q000187:drug effects* / Q000502:physiology; D022781:Hepatocytes / Q000166:cytology / Q000821:virology; D006801:Humans; D008715:Methionine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D017368:Protein Prenylation / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D014771:Virion; D019065:Virus Assembly / Q000187:drug effects*; D014779:Virus Replication
D004791:Enzyme Inhibitors; C096856:FTI 277; D008715:Methionine; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase