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Complete hepatitis B virus genome analysis in chronically infected children before and during lamivudine treatment
Author(s) -
Conzelmann Isabel,
Wintermeyer Philip,
Wirth Stefan,
Radke Robert,
Gerner Patrick
Publication year - 2005
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.20436
Subject(s) - lamivudine , virology , hepatitis b virus , nonsense mutation , mutation , mutation rate , biology , genome , hbsag , virus , genetics , resistance mutation , orthohepadnavirus , polymerase chain reaction , gene , missense mutation , reverse transcriptase
Abstract It is well established that during lamivudine treatment, mutations emerge within the polymerase gene but there is little information about the selection of other mutations in the whole hepatitis B virus (HBV) genome. The aim of this study was to investigate whether mutations outside this region are selected during lamivudine treatment. The complete HBV genomes of six HBsAg positive chronically infected children were isolated from the children's sera before, at the beginning and during lamivudine treatment, amplified and sequenced directly. A change in the mutation rate and type in periods with and without treatment for one and the same patient were examined longitudinally because blood samples were taken long before treatment started. During the testing period before treatment, 12 mutations occurred within 11.7 ± 8.1 months in all genomes, resulting in a mutation rate of 1.1 × 10 −3 substitutions per site per year. During treatment with lamivudine, 20 mutations occurred in all patients within an average period of 7.6 ± 1.2 months, giving an average mutation rate of 1.8 × 10 −3 substitutions per site per year. The 20 mutations observed during the treatment period occurred in only 4 of the patients and only 3 patients experienced nonsense mutations during lamivudine treatment. The mutations were spread across the entire genome with a non‐significant cluster during treatment in the P‐ORF (18 mutations vs. 7, P = 0.073) and S‐ORF (11 vs. 2, P = 0.063). Mutations causing drug resistance did not emerge. This study describes the changes in the complete HBV genome in the spontaneous course of infection and during lamivudine treatment. An increased mutation rate and the occurrence of specific mutations could not be proven for the early phase of lamivudine treatment. J. Med. Virol. 77:194–202, 2005. © 2005 Wiley‐Liss, Inc.