%0 Journal Article %A Wing Lam %A Ying Li %A Jieh-Yuan Liou %A Ginger E. Dutschman %A Yung-chi Cheng %T Reverse Transcriptase Activity of Hepatitis B Virus (HBV) DNA Polymerase within Core Capsid: Interaction with Deoxynucleoside Triphosphates and Anti-HBV l-Deoxynucleoside Analog Triphosphates %D 2004 %R 10.1124/mol.65.2.400 %J Molecular Pharmacology %P 400-406 %V 65 %N 2 %X The use of L(–)SddC [β-l-2′,3′-dideoxy-3′-thiacytidine (lamivudine, 3TC)] for the treatment of Herpes B virus (HBV) infection is hindered by the emergence of drug-resistance associated with the L526M, L550V, and L526M/M550V mutations of the viral DNA polymerase (DP). The interactions of the anti-HBV compounds 2′,3′-dideoxy-2′,3′-didehydro-β-l(–)-5-fluorode-oxycytidine and 2′-fluoro-5-methyl-β-l-arabinofuranosyluracil triphosphate with HBV DP and its L(–)SddC-associated mutants have not been studied. The e antigen-negative variant of HBV associated with the G1896A mutation in the precore region has a high prevalence. Its effect on HBV DP is unclear. Because HBV DNA synthesis occurs in the nucleocapsid, we examined the kinetics of the reverse transcriptase activity from wild-type (wt) and mutated DPs with the wt or G1896A-mutated RNA template in the nucleocapsid. The effects of this template mutation on the activities of these l-nucleoside triphosphates were also examined. Results indicated that these DP mutations increased the Km values of deoxy-NTPs and decreased the efficiencies (Vmax/Km) of DPs. The additional L526M mutation increased the efficiency of the M550V-mutated DP but no more than that of the L526M-mutated DP. The G1896A mutation had impacts on the interactions between different DPs and deoxy-NTPs, except dCTP. It also had different impacts on the actions of the l-nucleoside triphosphates toward DPs. The L526M and M550V mutations caused a greater decrease in the Vmax using the wt RNA template compared with the G1896A-mutated template. The L526M, M550V, and L526M/M550V mutations caused varying degrees of resistance to the different l-nucleoside triphosphates. %U https://molpharm.aspetjournals.org/content/molpharm/65/2/400.full.pdf