Dynamics of hepatitis B virus quasispecies in association with nucleos(t)ide analogue treatment determined by ultra-deep sequencing.
<h4>Background and aims</h4>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 hetero...
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2012
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oai:doaj.org-article:71ce1ca7b57f46bbb987a168b831bae72021-11-18T07:22:04ZDynamics of hepatitis B virus quasispecies in association with nucleos(t)ide analogue treatment determined by ultra-deep sequencing.1932-620310.1371/journal.pone.0035052https://doaj.org/article/71ce1ca7b57f46bbb987a168b831bae72012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22523569/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background and aims</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>Our findings illustrate the strong advantage of deep sequencing on viral genome as a tool for dissecting the pathophysiology of HBV infection.Norihiro NishijimaHiroyuki MarusawaYoshihide UedaKen TakahashiAkihiro NasuYukio OsakiTadayuki KouShujiro YazumiTakeshi FujiwaraSoken TsuchiyaKazuharu ShimizuShinji UemotoTsutomu ChibaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 4, p e35052 (2012) |
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Medicine R Science Q Norihiro Nishijima Hiroyuki Marusawa Yoshihide Ueda Ken Takahashi Akihiro Nasu Yukio Osaki Tadayuki Kou Shujiro Yazumi Takeshi Fujiwara Soken Tsuchiya Kazuharu Shimizu Shinji Uemoto Tsutomu Chiba Dynamics of hepatitis B virus quasispecies in association with nucleos(t)ide analogue treatment determined by ultra-deep sequencing. |
| description |
<h4>Background and aims</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>Our findings illustrate the strong advantage of deep sequencing on viral genome as a tool for dissecting the pathophysiology of HBV infection. |
| format |
article |
| author |
Norihiro Nishijima Hiroyuki Marusawa Yoshihide Ueda Ken Takahashi Akihiro Nasu Yukio Osaki Tadayuki Kou Shujiro Yazumi Takeshi Fujiwara Soken Tsuchiya Kazuharu Shimizu Shinji Uemoto Tsutomu Chiba |
| author_facet |
Norihiro Nishijima Hiroyuki Marusawa Yoshihide Ueda Ken Takahashi Akihiro Nasu Yukio Osaki Tadayuki Kou Shujiro Yazumi Takeshi Fujiwara Soken Tsuchiya Kazuharu Shimizu Shinji Uemoto Tsutomu Chiba |
| author_sort |
Norihiro Nishijima |
| title |
Dynamics of hepatitis B virus quasispecies in association with nucleos(t)ide analogue treatment determined by ultra-deep sequencing. |
| title_short |
Dynamics of hepatitis B virus quasispecies in association with nucleos(t)ide analogue treatment determined by ultra-deep sequencing. |
| title_full |
Dynamics of hepatitis B virus quasispecies in association with nucleos(t)ide analogue treatment determined by ultra-deep sequencing. |
| title_fullStr |
Dynamics of hepatitis B virus quasispecies in association with nucleos(t)ide analogue treatment determined by ultra-deep sequencing. |
| title_full_unstemmed |
Dynamics of hepatitis B virus quasispecies in association with nucleos(t)ide analogue treatment determined by ultra-deep sequencing. |
| title_sort |
dynamics of hepatitis b virus quasispecies in association with nucleos(t)ide analogue treatment determined by ultra-deep sequencing. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2012 |
| url |
https://doaj.org/article/71ce1ca7b57f46bbb987a168b831bae7 |
| work_keys_str_mv |
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