ArticleThe Journal of clinical investigation2001
The polymerase L528M mutation cooperates with nucleotide binding-site mutations, increasing hepatitis B virus replication and drug resistance.
Article in The Journal of clinical investigation, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed, 272 citations in OpenAlex.
- Two-year assessment of entecavir resistance in Lamivudine-refractory hepatitis B virus patients reveals different clinical outcomes depending on the resistance substitutions present.Antimicrobial agents and chemotherapy · 2007Trial
- Clinical pharmacokinetics of alamifovir and its metabolites.Antimicrobial agents and chemotherapy · 2005Trial
- Strategies and efforts in circumventing the emergence of antiviral resistance against conventional antivirals.npj antimicrobials and resistance · 2025Review
- Hepatitis B x antigen (HBx) is an important therapeutic target in the pathogenesis of hepatocellular carcinoma.Oncotarget · 2021Article
- Moving Fast Toward Hepatitis B Virus Elimination.Advances in experimental medicine and biology · 2021Article
- HBx mutations emerged during antiviral therapy: a new face of a multifaceted HBV protein?Hepatology international · 2020Article
- Coevolution analysis of amino-acids reveals diversified drug-resistance solutions in viral sequences: a case study of hepatitis B virus.Virus evolution · 2020Article
- Regulation Between HSF1 Isoforms and HSPs Contributes to the Variation in Thermal Tolerance Between Two Oyster Congeners.Frontiers in genetics · 2020Article
- Naturally occurring core protein mutations compensate for the reduced replication fitness of a lamivudine-resistant HBV isolate.Antiviral research · 2019Article
- Long-term outcome of entecavir treatment of nucleos(t)ide analogue-naïve chronic hepatitis B patients in Japan.Journal of gastroenterology · 2019Article
- Long-term virological and adherence outcomes to antiviral treatment in a 4-year cohort chronic HBV study.Antiviral therapy · 2019Article
- No Resistance to Tenofovir Alafenamide Detected through 96 Weeks of Treatment in Patients with Chronic Hepatitis B Infection.Antimicrobial agents and chemotherapy · 2018Article
- Prevalence of hepatitis B antiviral drug resistance variants in North American patients with chronic hepatitis B not receiving antiviral treatment.Journal of viral hepatitis · 2017Article
- Overview of hepatitis B viral replication and genetic variability.Journal of hepatology · 2016Review
- Assessment of Adherence to Prescribed Therapy in Patients with Chronic Hepatitis B.Infectious diseases and therapy · 2016Article
- Long-term outcomes and dynamics of mutants associated with lamivudine-adefovir rescue therapy in patients with lamivudine-resistant chronic hepatitis B.Gut and liver · 2015Article
- Management of antiviral drug resistance in chronic hepatitis B.World journal of gastroenterology · 2014Review
- Analysis of reverse transcriptase gene mutations in the hepatitis B virus at a university hospital in Korea.Annals of laboratory medicine · 2014Article
- An initial assessment of correlations between host- and virus-related factors affecting analogues antiviral therapy in HBV chronically infected patients.Medical science monitor : international medical journal of experimental and clinical research · 2014Article
- High-throughput matrix-assisted laser desorption ionization-time of flight mass spectrometry as an alternative approach to monitoring drug resistance of hepatitis B virus.Journal of clinical microbiology · 2014Article
18 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 3 countries.
Funding
Abstract
After receiving lamivudine for 3 years to treat chronic hepatitis B, 67-75% of patients develop B-domain L528M, C-domain M552I, or M552V mutations in the HBV polymerase that render hepatitis B virus (HBV) drug-resistant. The aim of this study was to evaluate the influence of these mutations on viral replication and resistance to antiviral agents. We investigated the replication fitness and susceptibility of the wild-type and five mutant HBVs (L528M, M552I, M552V, L528M/M552I, and L528M/M552V) to 11 compounds [lamivudine, adefovir, entecavir (BMS-200475) (+)-BCH-189 (+/-)-FTC (racivir) (-)-FTC (emtricitabine) (+)-FTC, L-D4FC, L-FMAU (clevudine), D-DAPD, and (-)-carbovir] by transfecting HBV DNA into hepatoma cells and monitoring viral products by Southern blotting. The replication competency of the single C-domain mutants M552I and M552V was markedly decreased compared with that of wild-type HBV. However, addition of the B-domain mutation L528M restored replication competence. Only adefovir and entecavir were effective against all five HBV mutants, and higher doses of these compounds were necessary to inhibit the double mutants compared with the single mutants. The B-domain mutation (L528M) of HBV polymerase not only restores the replication competence of C-domain mutants, but also increases resistance to nucleoside analogues.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.