Supportive role played by precore and preS2 genomic changes in the establishment of lamivudine-resistant hepatitis B virus

The Journal of Infectious Diseases
Kazuyoshi OhkawaNorio Hayashi

Abstract

Hepatitis B virus (HBV) establishes lamivudine resistance via the resistance-causative rtM204V/I mutation and the replication-compensatory rtL180M mutation. However, both lamivudine-resistant viruses with and those without rtL180M can exist in clinical settings. To elucidate the differences between viruses with and those without rtL180M, we conducted full-length sequencing analysis of HBV derived from patients with type B chronic hepatitis showing lamivudine resistance. The full-length HBV DNA sequences derived from 44 patients showing lamivudine resistance were determined by polymerase chain reaction direct sequencing. Viral replicative competence was examined by in vitro transfection analysis using various HBV-expressing plasmids. Throughout the HBV genome, a precore-defective A1896 mutation and a short deletion in the preS2 gene were detected more frequently in viruses without rtL180M than in those with it (64% vs. 17% [P < .005] and 50% vs. 10% [P < .01], respectively). In vitro transfection analysis revealed that the level of reduction in intracellular viral replication caused by the introduction of lamivudine resistance-associated mutations was lower in precore-defective and preS2-deleted viruses than in wild-type virus. ...Continue Reading

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Citations

Mar 11, 2010·Biochemical and Biophysical Research Communications·Kazuyoshi OhkawaNorio Hayashi
May 8, 2014·Journal of Hepatology·Teresa PollicinoGiovanni Raimondo
Feb 24, 2010·Biochemical and Biophysical Research Communications·Kazuyoshi OhkawaNorio Hayashi

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