Hepatitis B virus (HBV) replication is mediated by the effective vaccines against hepatitis B virus (HBV) usviral polymerase that possesses three functional doing surface antigens have been developed, there are mains: primer, DNA polymerase/reverse transcriptase, still approximately 300 million carriers worldwide. 1 Beand RNase H. Using the Pekin duck as an animal model, cause the vaccine is of no benefit for the carriers, an we demonstrate a novel mechanism of inhibition of duck attempt to find antiviral agents to treat chronic carrihepatitis B virus (DHBV) by 2,6-diaminopurine 2,3-diers is justified. Unfortunately, antiviral therapy deoxyriboside (ddDAPR), a prodrug of 2,3-dideoxyguaagainst HBV infection has met with very limited sucnosine (ddG). A selective and irreversible inhibition of cess. [2][3][4][5] Recently, several nucleoside analogs have been
DHBV DNA replication is found in ducklings treated
shown to be effective inhibitors of hepadnaviral replicawith high doses of ddDAPR (20 to 50 mg/kg), but not with tion, 6-9 but the mechanism of action of these agents similar doses of 2,3-dideoxycytidine (ddC). The inhibition mediated by ddDAPR occurs at a very early stage remains unclear.
of the reverse transcription. Despite the inhibition of HBV is a partially double-stranded DNA virus with DHBV DNA replication by ddDAPR, the DNA polymera genome length of approximately 3,200 nucleotides. ase and reverse transcriptase activities of the polymer-Viral DNA synthesis, which is mediated by the viral ase are found to remain active when tested on exogenous polymerase, involves two stages: the synthesis of minus templates in activity gels. We have demonstrated direct strand DNA by reverse transcription using the prebinding of [a-32 P]ddGTP to the DHBV polymerase exgenomic RNA as template, and the synthesis of plus pressed in an in vitro transcription and translation sysstrand DNA using the newly synthesized minus strand tem. These results suggest that the binding of ddGTP to DNA as template. [10][11][12] Initiation of minus strand DNA the polymerase blocks the initial DNA replication. (HEPsynthesis has been shown to be mediated by a primer