Effect of tenofovir disoproxil fumarate on drug-resistant HBV clones
Tenofovir disoproxil fumarate (TDF) has been approved for chronic hepatitis B treatment, and favorable susceptibility of hepatitis B virus (HBV) has been indicated. However, differences in TDF susceptibility among HBV genotypes and drug-resistant strains are unclear. In this study, TDF susceptibilities between genotypes A and C were evaluated in vitro and in vivo using several drug-resistant HBV clones. HBV expression plasmids were constructed from sera of HBV carriers, and drug-resistant substitutions were introduced by site-directed mutagenesis. TDF susceptibility was evaluated by changes of core-associated HBV replication intermediates in vitro or by change of serum HBV DNA in human hepatocyte chimeric mice carrying each HBV clone in vivo. TDF susceptibilities of lamivudine-resistant clones (rtL180M/M204V) and lamivudine plus entecavir-resistant clones (rtL180M/S202G/M204V) were similar to wild type clones in vitro. However, lamivudine plus adefovir-resistant clones (rtA181T/N236T) acquired tolerance to TDF, and the rtN236T mutation was considered to be a causal substitution for TDF resistance. Furthermore, genotypic differences in TDF susceptibility were also observed between genotypes A and C in vitro, and the differences could be confirmed in vivo (p = 0.023). The present study indicates that TDF susceptibility varies among HBV genotypes and drug-resistant HBV clones..
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2016 |
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| Erschienen: |
2016 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:72 |
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| Enthalten in: |
Journal of infection - 72(2016), 1, Seite 91 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Murakami, Eisuke [VerfasserIn] |
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| Links: |
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| RVK: |
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| doi: |
10.1016/j.jinf.2015.09.038 |
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| 520 | |a Tenofovir disoproxil fumarate (TDF) has been approved for chronic hepatitis B treatment, and favorable susceptibility of hepatitis B virus (HBV) has been indicated. However, differences in TDF susceptibility among HBV genotypes and drug-resistant strains are unclear. In this study, TDF susceptibilities between genotypes A and C were evaluated in vitro and in vivo using several drug-resistant HBV clones. HBV expression plasmids were constructed from sera of HBV carriers, and drug-resistant substitutions were introduced by site-directed mutagenesis. TDF susceptibility was evaluated by changes of core-associated HBV replication intermediates in vitro or by change of serum HBV DNA in human hepatocyte chimeric mice carrying each HBV clone in vivo. TDF susceptibilities of lamivudine-resistant clones (rtL180M/M204V) and lamivudine plus entecavir-resistant clones (rtL180M/S202G/M204V) were similar to wild type clones in vitro. However, lamivudine plus adefovir-resistant clones (rtA181T/N236T) acquired tolerance to TDF, and the rtN236T mutation was considered to be a causal substitution for TDF resistance. Furthermore, genotypic differences in TDF susceptibility were also observed between genotypes A and C in vitro, and the differences could be confirmed in vivo (p = 0.023). The present study indicates that TDF susceptibility varies among HBV genotypes and drug-resistant HBV clones. | ||
| 540 | |a Nutzungsrecht: Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved. | ||
| 700 | 1 | |a Tsuge, Masataka |4 oth | |
| 700 | 1 | |a Hiraga, Nobuhiko |4 oth | |
| 700 | 1 | |a Kan, Hiromi |4 oth | |
| 700 | 1 | |a Uchida, Takuro |4 oth | |
| 700 | 1 | |a Masaki, Keiichi |4 oth | |
| 700 | 1 | |a Nakahara, Takashi |4 oth | |
| 700 | 1 | |a Ono, Atsushi |4 oth | |
| 700 | 1 | |a Miki, Daiki |4 oth | |
| 700 | 1 | |a Kawaoka, Tomokazu |4 oth | |
| 700 | 1 | |a Abe, Hiromi |4 oth | |
| 700 | 1 | |a Imamura, Michio |4 oth | |
| 700 | 1 | |a Aikata, Hiroshi |4 oth | |
| 700 | 1 | |a Ochi, Hidenori |4 oth | |
| 700 | 1 | |a Hayes, C Nelson |4 oth | |
| 700 | 1 | |a Akita, Tomoyuki |4 oth | |
| 700 | 1 | |a Tanaka, Junko |4 oth | |
| 700 | 1 | |a Chayama, Kazuaki |4 oth | |
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