Glenn J S, Marsters J C, Greenberg H B
Division of Gastroenterology, Stanford University School of Medicine and Veterans Administration Medical Center, Palo Alto, California 94305-5487, USA.
J Virol. 1998 Nov;72(11):9303-6. doi: 10.1128/JVI.72.11.9303-9306.1998.
No specific therapy exists for hepatitis delta virus (HDV), which can cause severe liver disease. Molecular genetic studies have implicated the prenylation site of large delta antigen as a critical determinant of HDV particle assembly. We have established a cell culture model which produces HDV-like particles, and we show that delta antigen prenylation can be pharmacologically inhibited by the prenylation inhibitor BZA-5B. Furthermore, BZA-5B specifically abolishes particle production in a dose-dependent manner. These results demonstrate that the use of such a prenylation inhibitor-based antiviral therapy may be feasible and identify a novel class of potential antiviral agents.
目前尚无针对可导致严重肝脏疾病的丁型肝炎病毒(HDV)的特异性疗法。分子遗传学研究表明,大丁型抗原的异戊二烯化位点是HDV颗粒组装的关键决定因素。我们建立了一种可产生HDV样颗粒的细胞培养模型,并且我们发现异戊二烯化抑制剂BZA-5B可在药理学上抑制丁型抗原的异戊二烯化。此外,BZA-5B以剂量依赖性方式特异性消除颗粒产生。这些结果表明,使用这种基于异戊二烯化抑制剂的抗病毒疗法可能是可行的,并确定了一类新型潜在抗病毒药物。