ArticleAntimicrobial agents and chemotherapy2006
Emergence of a novel lamivudine-resistant hepatitis B virus variant with a substitution outside the YMDD motif.
Article in Antimicrobial agents and chemotherapy, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
- Hepatitis B virus resistance to tenofovir: fact or fiction? A systematic literature review and structural analysis of drug resistance mechanisms.Wellcome open research · 2020Pooled it
- Importance of serum concentration of adefovir for Lamivudine-adefovir combination therapy in patients with lamivudine-resistant chronic hepatitis B.Antimicrobial agents and chemotherapy · 2010Trial
- Diagnostic challenges due to hepatitis B virus surface antigen mutations outside the major hydrophilic region.Archives of virology · 2025Article
- Spacer Domain in Hepatitis B Virus Polymerase: Plugging a Hole or Performing a Role?Journal of virology · 2022Review
- Are Humanized Mouse Models Useful for Basic Research of Hepatocarcinogenesis through Chronic Hepatitis B Virus Infection?Viruses · 2021Review
- Roles of Hepatitis B Virus Mutations in the Viral Reactivation after Immunosuppression Therapies.Viruses · 2019Review
- No Resistance to Tenofovir Alafenamide Detected through 96 Weeks of Treatment in Patients with Chronic Hepatitis B Infection.Antimicrobial agents and chemotherapy · 2018Article
- Discovery of the Novel Entecavir-Resistant Hepatitis B Virus Reverse Transcriptase A181C Substitution From an Integrated Genotypic Analysis.Hepatology communications · 2018Article
- Development of a Novel Site-Specific Pegylated Interferon Beta for Antiviral Therapy of Chronic Hepatitis B Virus.Antimicrobial agents and chemotherapy · 2017Article
- Biological characteristics comparison of HBV rtA181T mutants with truncated or substituted HBsAg expression in vitro and in vivo model systems.Scientific reports · 2016Article
- Genetic variation of hepatitis B virus and its significance for pathogenesis.World journal of gastroenterology · 2016Review
- Mouse models of hepatitis B virus infection comprising host-virus immunologic interactions.Pathogens (Basel, Switzerland) · 2014Review
- rtM204Q may serve as a novel lamivudine-resistance-associated mutation of hepatitis B virus.PloS one · 2014Article
- Epidemiological, virological and clinical characteristics of HBV infection in 223 HIV co-infected patients: a French multi-centre collaborative study.Virology journal · 2013Article
- Experimental models and therapeutic approaches for HBV.Seminars in immunopathology · 2013Review
- Clonal evolution of hepatitis B virus polymerase gene mutations during lamivudine-adefovir combination treatment.World journal of gastroenterology · 2012Article
- Biological characteristics of the rtA181T/sW172* mutant strain of Hepatitis B virus in animal model.Virology journal · 2012Article
- Telbivudine in combination with adefovir versus adefovir monotherapy in HBeAg-positive, lamivudine-resistant chronic hepatitis B.Hepatology international · 2012Article
- Molecular epidemical characteristics of Lamivudine resistance mutations of HBV in southern China.Medical science monitor : international medical journal of experimental and clinical research · 2011Article
- Human microRNA hsa-miR-125a-5p interferes with expression of hepatitis B virus surface antigen.Nucleic acids research · 2011Article
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lamivudine is a major drug approved for treatment of chronic hepatitis B virus (HBV) infection. Emergence of drug-resistant mutants with amino acid substitutions in the YMDD motif is a well-documented problem during long-term lamivudine therapy. Here we report a novel lamivudine-resistant strain of HBV with an intact YMDD motif, which included an amino acid substitution, rtA181T, in the reverse transcriptase (RT) domain of HBV polymerase. The substitution also induced a unique amino acid substitution (W172L) in the overlapping hepatitis B surface (HBs) protein. The YMDD mutant strains were not detected even by using the sensitive peptide nucleic acid-mediated PCR clamping method. The detected nucleotide substitution was accompanied by the emergence of an additional nucleotide substitution that induced amino acid change (S331C) in the spacer domain. The rtA181T mutant strain displayed a threefold decrease in susceptibility to lamivudine in in vitro experiments in comparison with the wild type. In vivo analysis using human hepatocyte-chimeric mice confirmed the resistance of this mutant strain to lamivudine. We developed a method to detect this novel rtA181T mutation and a previously reported rtA181T mutation with the HBs stop codon using restriction fragment length polymorphism PCR and identified one patient with the latter pattern among 40 patients with lamivudine resistance. In conclusion, although the incidence is not high, we have to be careful regarding the emergence of lamivudine-resistant mutant strains with intact YMDD motif.
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