The Study Of Genes And Structures Of HBV Influencing The Efficiency Of Nucleoside Analogue Drug

Objective: To study the mechanism of HBV resistance to nucleoside analoguedrug.Methods: P gene of HBV was amplified by one step PCR in serums beforetreatment, a year after lamivudine treatment and a year after adefovir treatment from apatient of CHB with HBV resistant to both lamivudine and adefovir, then cloned andsequenced and compared with the sequences in Genbank.Result: 1. Genotype B was determined in serums before therapy and one yearafter adiefovir-therapy; and genotype C in the serum one year afterlamivudine-therapy. 2. In the serum one year after lamivudine-therapy, a G-to-Tchange at nucleotide 743(G743T) was found in P gene, leading to rtM204I resistant. Adouble mutation of rtP91L and rtC256S in domains A and E was also observed.Besides, there were ten amino acid substitutions in the polymerase. 3. A deletion of 61amino acids was found in the spacer domain of polymerase gene in the serum oneyear after adefovir-therapy. In addition, five amino acid substitutions were alsodetected in the polymerase gene..Conclusion: 1. The genotype of HBV might change during the course of thenucleoside analogue treatment. 2. RtM204I mutant in the YMDD motif was one of themain reasons of HBV resistance to lamivudine. 3. A deletion of large segment inspacer domain might be in correlated with HBV resistance to adiefovir, and it isworthy to be further conformed.