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Title: | Dynamics of Hepatitis B Virus Quasispecies in Association with Nucleos(t)ide Analogue Treatment Determined by Ultra-Deep Sequencing. |
Authors: | Nishijima, Norihiro Marusawa, Hiroyuki ![]() ![]() Ueda, Yoshihide ![]() ![]() ![]() Takahashi, Ken ![]() ![]() Nasu, Akihiro Osaki, Yukio Kou, Tadayuki Yazumi, Shujiro Fujiwara, Takeshi Tsuchiya, Soken Shimizu, Kazuharu Uemoto, Shinji ![]() ![]() Chiba, Tsutomu ![]() ![]() |
Author's alias: | 西島, 規浩 丸澤, 宏之 |
Issue Date: | 16-Apr-2012 |
Publisher: | Public Library of Science |
Journal title: | PloS one |
Volume: | 7 |
Issue: | 4 |
Thesis number: | e35052 |
Abstract: | [Background and Aims]: Although the advent of ultra-deep sequencing technology allows for the analysis of heretofore-undetectable minor viral mutants, a limited amount of information is currently available regarding the clinical implications of hepatitis B virus (HBV) genomic heterogeneity. [Methods]: To characterize the HBV genetic heterogeneity in association with anti-viral therapy, we performed ultra-deep sequencing of full-genome HBV in the liver and serum of 19 patients with chronic viral infection, including 14 therapy-naïve and 5 nucleos(t)ide analogue(NA)-treated cases. [Results]: Most genomic changes observed in viral variants were single base substitutions and were widely distributed throughout the HBV genome. Four of eight (50%) chronic therapy-naïve HBeAg-negative patients showed a relatively low prevalence of the G1896A pre-core (pre-C) mutant in the liver tissues, suggesting that other mutations were involved in their HBeAg seroconversion. Interestingly, liver tissues in 4 of 5 (80%) of the chronic NA-treated anti-HBe-positive cases had extremely low levels of the G1896A pre-C mutant (0.0%, 0.0%, 0.1%, and 1.1%), suggesting the high sensitivity of the G1896A pre-C mutant to NA. Moreover, various abundances of clones resistant to NA were common in both the liver and serum of treatment-naïve patients, and the proportion of M204VI mutants resistant to lamivudine and entecavir expanded in response to entecavir treatment in the serum of 35.7% (5/14) of patients, suggesting the putative risk of developing drug resistance to NA. [Conclusion]: Our findings illustrate the strong advantage of deep sequencing on viral genome as a tool for dissecting the pathophysiology of HBV infection. |
Rights: | © 2012 Nishijima et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
URI: | http://hdl.handle.net/2433/155467 |
DOI(Published Version): | 10.1371/journal.pone.0035052 |
PubMed ID: | 22523569 |
Appears in Collections: | Journal Articles |

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