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dc.contributor.author | Nishijima, Norihiro | en |
dc.contributor.author | Marusawa, Hiroyuki | en |
dc.contributor.author | Ueda, Yoshihide | en |
dc.contributor.author | Takahashi, Ken | en |
dc.contributor.author | Nasu, Akihiro | en |
dc.contributor.author | Osaki, Yukio | en |
dc.contributor.author | Kou, Tadayuki | en |
dc.contributor.author | Yazumi, Shujiro | en |
dc.contributor.author | Fujiwara, Takeshi | en |
dc.contributor.author | Tsuchiya, Soken | en |
dc.contributor.author | Shimizu, Kazuharu | en |
dc.contributor.author | Uemoto, Shinji | en |
dc.contributor.author | Chiba, Tsutomu | en |
dc.contributor.alternative | 西島, 規浩 | ja |
dc.contributor.alternative | 丸澤, 宏之 | ja |
dc.date.accessioned | 2012-05-09T02:52:24Z | - |
dc.date.available | 2012-05-09T02:52:24Z | - |
dc.date.issued | 2012-04-16 | - |
dc.identifier.issn | 1932-6203 | - |
dc.identifier.uri | http://hdl.handle.net/2433/155467 | - |
dc.description.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. | en |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Public Library of Science | en |
dc.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. | en |
dc.title | Dynamics of Hepatitis B Virus Quasispecies in Association with Nucleos(t)ide Analogue Treatment Determined by Ultra-Deep Sequencing. | en |
dc.type | journal article | - |
dc.type.niitype | Journal Article | - |
dc.identifier.jtitle | PloS one | en |
dc.identifier.volume | 7 | - |
dc.identifier.issue | 4 | - |
dc.relation.doi | 10.1371/journal.pone.0035052 | - |
dc.textversion | publisher | - |
dc.identifier.artnum | e35052 | - |
dc.identifier.pmid | 22523569 | - |
dcterms.accessRights | open access | - |
出現コレクション: | 学術雑誌掲載論文等 |
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