Molecular biology of hepatitis D virus: research and potential for application.
Superinfection by hepatitis D virus (HDV) leads to acute hepatitis and causes progression to liver cirrhosis in a significant proportion of hepatitis B surface antigen (HBsAg) carriers. Current regimens (interferon) to treat hepatitis D patients has only transient but no lasting effects. New approaches are, therefore, warranted. Recently, several laboratory studies have discovered interesting properties of HDV that may become targets for antiviral chemicals. Viral replication requires the small hepatitis delta antigen (s-HDAg). The s-HDAg is a nuclear phosphoprotein. There is evidence indicating that phosphorylation is important for HDV replication. A second step of replication requires HDV-RNA self-cleavage and self-ligation. Interestingly, one group of antibiotics, the aminoglycosides, exerts strong suppression effects on HDV ribozyme activities. In the following stage of viral assembly, two post-translational modifications, namely isoprenylation of large HDAg and glycosylation of HBsAg are involved. Agents capable of blocking the two modifications should reduce viral production. These four possible targets are reviewed. For prevention, effective vaccines are not yet available. Two novel approaches are discussed. The first demonstrates the immunogenicity of a nucleic acid vaccine in mice. The second approach assembled an empty HDV particle in yeast. Advances on such laboratory investigations may provide new methods for the control of hepatitis D in the future.
Chen
P J
PJ
Graduate Institute of Clinical Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Wu
H L
HL
Wang
C J
CJ
Chia
J H
JH
Chen
D S
DS
D000617:Aminoglycosides / Q000494:pharmacology; D000818:Animals; D003699:Hepatitis D / Q000517:prevention & control; D003698:Hepatitis Delta Virus / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D006801:Humans; D016337:RNA, Catalytic / Q000037:antagonists & inhibitors / Q000378:metabolism; D014765:Viral Vaccines / Q000627:therapeutic use; D014773:Virology / Q000639:trends
D000617:Aminoglycosides; D016337:RNA, Catalytic; D014765:Viral Vaccines