YSDD: a novel mutation in HBV DNA polymerase confers clinical resistance to lamivudine
| Jazyk: | English |
|---|---|
| Přístupová URL adresa: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e8d21d4eb012cdaab16727c3a5ac67fe https://avesis.gazi.edu.tr/publication/details/80d42777-5612-42e9-964c-74113c65e920/oai |
| Rights: | CLOSED |
| Přírůstkové číslo: | edsair.doi.dedup.....e8d21d4eb012cdaab16727c3a5ac67fe |
| Autor: | Hakan Bozkaya, O. Sezgin, N. Aslan, Kubilay Cinar, Selim Karayalcin, Rekha B Pai, Cihan Yurdaydin, Gulendam Bozdayi, Raymond F. Schinazi, T. Sahin, Ozden Uzunalimoglu, A.R. Turkyilmaz, A.M. Bozdayi, S. B. Pai |
| Jazyk: | angličtina |
| Rok vydání: | 2003 |
| Předmět: |
Adult
Male Hepatitis B virus Genotype Base pair Molecular Sequence Data Gene Products pol DNA-Directed DNA Polymerase medicine.disease_cause Antiviral Agents Polymerase Chain Reaction Sensitivity and Specificity Virus law.invention chemistry.chemical_compound Hepatitis B Chronic law Interferon Reference Values Virology Drug Resistance Viral medicine Humans Polymerase chain reaction Aged Mutation Methionine Hepatology Base Sequence business.industry Lamivudine virus diseases Middle Aged Molecular biology Infectious Diseases chemistry Pharmacogenetics DNA Viral Female business medicine.drug |
| Popis: | The emergence of drug-resistant virus in hepatitis B virus (HBV) patients treated with lamivudine is well documented. In this study, we determined the mutations occurring in the tyrosine-methionine-aspartate-aspartate (YMDD) amino acid motif of the HBV DNA polymerase gene, as well as upstream and downstream of this region, in patients with breakthrough virus during lamivudine therapy. Thirty-one Turkish patients (20 patients HBeAg positive, 11 patients HBeAg negative and anti-HBe positive) with chronic HBV infection who completed at least 104 weeks of lamivudine treatment were investigated. All patients received lamivudine, (150 mg/day), for 104 weeks, with or without 4 months of interferon (IFN) combination. HBV-specific sequences were amplified by polymerase chain reaction (PCR) from sera of patients with breakthrough virus, and the PCR products were directly analysed by sequencing. Breakthrough virus was detected in seven of the 31 patients (22.6%) between 9 and 18 months of therapy. Of the seven patients, six were HBeAg positive at baseline, and four had a double mutation consisting of rtM204V and rtL180M, while two had an rtM204I change. In one patient, two base substitutions at rt204 (ATG --> AGT; T to G and G to T) lead to a methionine to serine change (YMDD --> YSDD). This novel DNA pol mutation was detected at month 18 of lamivudine treatment. In addition, this new variant had the rtL180M mutation and a 12 base pair deletion in the pre-S1 region between nucleotides 43-54. The YSDD mutation was still present 6 months after lamivudine discontinuation. In vitro transfection studies also confirmed that the YSDD strain is resistant to lamivudine. In conclusion, the results indicate that, in addition to a Met --> Val and Met --> Ile change in YMDD, a Met --> Ser change at rt204 (YMDD --> YSDD) associated with the rtL180M change can also emerge during lamivudine treatment, which confers lamivudine resistance in vivo and in vitro, leading to virological breakthrough and ALT increases. |
| Databáze: | OpenAIRE |
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