Molecular modeling and biochemical characterization reveal the mechanism of hepatitis B virus polymerase resistance to lamivudine (3TC) and emtricitabine (FTC).
Abstract: Specifically, steric conflict between the Cgamma2-methyl group of Ile or Val at position 552 in HBV polymerase and the sulfur atom in the oxathiolane ring (common to both beta-L-nucleoside analogs lamivudine and emtricitabine) is proposed to account for the resistance observed upon Met552Ile/Val mutation.
Abstract: The effects of Leu528Met, Met552Ile, and Met552Val mutations on the binding of HBV polymerase inhibitors and the natural substrate dCTP were evaluated using an in vitro HBV polymerase assay.
Abstract: The predominant lamivudine resistance mutations in HBV-infected patients are Met552IIe and Met552Val (Met552Ile/Val), frequentl
Detection of hepatitis B virus resistance to antivirals.
Abstract: Sequence analysis of the reverse transcriptase domain of resistant viral strains, at the time of viral breakthrough, revealed the occurrence of mutations located in the YMDD motif within the C domain of the viral enzyme with a methionine to valine (M552V) or to isoleucine (M5521) change.
Abstract: The lamivudine resistant mutants, selected in vivo, can be classified in 2 main groups: group I with a double mutation L528M and M552V, and group II with a single mutation M5521.
Factors associated with hepatitis B virus DNA breakthrough in patients receiving prolonged lamivudine therapy.
Abstract: Patients with HBV DNA breakthroughs had higher percentages of YMDD variants without the presence of wild-type YMDD compared with patients without HBV DNA breakthrough (25.6% vs. 9%, P =.007 for single M552I variant; 20.9% vs. 8.1%, P =.026 for single M552V variant; 30.2% vs. 9.9%, P =.004 for M552I/M552V variants). Patients with HBV DNA levels of more than 10(3) copies/mL after 6 months of lamivudine therapy had a 63.2% chance of subsequently developing YMDD variants.
Early detection of viral resistance by determination of hepatitis B virus polymerase mutations in patients treated by lamivudine for chronic hepatitis B.
Abstract: Determination of viral genotype, precore mutants, and polymerase gene mutants (L528M, M552V, M552I) was performed using the research version of Lipa-HBV.
Genotypic succession of mutations of the hepatitis B virus polymerase associated with lamivudine resistance.
Abstract: CONCLUSION: Our observations show that the virus populations conferring resistance to lamivudine can evolve from single to double mutations at amino acid 552 and 528 of the HBV polymerase, and that M552I/ L528M or M552V/L528M seem to be the predominant mutations arising during long-term antiviral therapy with lamivudine.
Abstract: In the majority of lamivudine-resistant isolates the mutations have been reported to occur within the YMDD motif of the viral polymerase, either as a single mutation M552I or as M552V concomitant with L528M.
Abstract: RESULTS: Genotypic succession of the virus populations was observed to occur f
Clearance of the original hepatitis B virus YMDD-motif mutants with emergence of distinct lamivudine-resistant mutants during prolonged lamivudine therapy.
Abstract: Of the 23 patients included, 13 harbored either one or a mixture of the two common YMDD-motif mutants (methionine 552-to-isoleucine [M552I] and leucine 528-to-methionine/methionine 552-to-valine [L528M/M552V]) throughout the course, whereas in the remaining 10 patients, distinct mutants became dominant over the original mutants to cause continuing chronic hepatitis.
Line probe assay for monitoring drug resistance in hepatitis B virus-infected patients during antiviral therapy.
PMID: 10655370
2000
Journal of clinical microbiology
Abstract: A set of 38 highly specific oligonucleotide probes covering three different codon positions, L528M, M552V/I, and V/L/M555I, were selected.
In vitro evaluation of hepatitis B virus polymerase mutations associated with famciclovir resistance.
Abstract: The lamivudine-resistant mutations M552I, M552V, and L528M+M552V, which were previously shown to display 8- to 25-fold resistance to LAMTP, were less resistant (< or = 3.1-fold) to PCVTP.
Mutational pattern of hepatitis B virus on sequential therapy with famciclovir and lamivudine in patients with hepatitis B virus reinfection occurring under HBIg immunoglobulin after liver transplantation.
Abstract: However, 7 patients developed a breakthrough within 12, 29 (n = 2), 32, 37, 54, and 145 weeks under treatment with LAM associated with the methionine-to-valine signature mutation (M552V) in the YMDD motif in all.
Perspectives for the treatment of hepatitis B virus infections.
PMID: 10418752
1999
International journal of antimicrobial agents
Abstract: L528M and M552V/I) in the HBV DNA polymerase upon long-term treatment.
HBV mutation literature information.
PMID: 
2001
Journal of virology
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