Testing Antivirals Against Hepatitis Delta Virus: Farnesyl Transferase Inhibitors
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Since the discovery of hepatitis delta virus (HDV) about 25 yr ago ( 1 – 3 ), no medical therapy has yet been developed to eradicate effectively this cause of acute and chronic liver disease. This small RNA virus is composed of three main elements: a 1.7-kb circular single-stranded RNA genome, two isoforms of an antigenome-encoded protein—the delta antigens—and a lipid envelope embedded with hepatitis B virus (HBV) surface antigens (HBsAgs) (Fig. 1 [ 4 , 5 ]). These latter proteins are necessary for the production of infectious HDV particles, which explains why clinical infections with HDV occur only in the presence of an HBV infection. The presence of HDV can dramatically increase the severity of the underlying HBV infection ( 6 – 8 ). Clearance of delta infections is refractory to interferon ( 9 ), and recent improved therapies that clear HBV viremia but still fail to abolish HBsAg levels have no impact on HDV ( 10 ). Thus other anti-HDV strategies need to be considered.
Fig. 1. Schematic overview showing the principal structural elements of a HDV particle: genomic circular RNA, complexed with delta antigen (large and small), is surrounded by a lipid envelope embedded with HBV surface antigen proteins. (The precise stoichiometry is not known and simplified here for illustrative purposes.)
