Large-scale viral genome analysis identifies novel clinical associations between hepatitis B virus and chronically infected patients
Abstract Despite the high global prevalence of chronic hepatitis B (CHB) infection, datasets covering the whole hepatitis B viral genome from large patient cohorts are lacking, greatly limiting our understanding of the viral genetic factors involved in this deadly disease. We performed deep sequenci...
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Nature Portfolio
2019
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oai:doaj.org-article:8a1e909a6e354d32b320dc74b869d6492021-12-02T15:07:54ZLarge-scale viral genome analysis identifies novel clinical associations between hepatitis B virus and chronically infected patients10.1038/s41598-019-46609-72045-2322https://doaj.org/article/8a1e909a6e354d32b320dc74b869d6492019-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-46609-7https://doaj.org/toc/2045-2322Abstract Despite the high global prevalence of chronic hepatitis B (CHB) infection, datasets covering the whole hepatitis B viral genome from large patient cohorts are lacking, greatly limiting our understanding of the viral genetic factors involved in this deadly disease. We performed deep sequencing of viral samples from patients chronically infected with HBV to investigate the association between viral genome variation and patients’ clinical characteristics. We discovered novel viral variants strongly associated with viral load and HBeAg status. Patients with viral variants C1817T and A1838G had viral loads nearly three orders of magnitude lower than patients without those variants. These patients consequently experienced earlier viral suppression while on treatment. Furthermore, we identified novel variants that either independently or in combination with precore mutation G1896A were associated with the transition from HBeAg positive to the negative phase of infection. These observations are consistent with the hypothesis that mutation of the HBeAg open reading frame is an important factor driving CHB patient’s HBeAg status. This analysis provides a detailed picture of HBV genetic variation in the largest patient cohort to date and highlights the diversity of plausible molecular mechanisms through which viral variation affects clinical phenotype.Ondrej PodlahaEdward GaneMaurizia BrunettoScott FungWan-Long ChuangCalvin Q. PanZhaoshi JiangYang LiuNeeru BhardwajPrasenjit MukherjeeJohn FlahertyAnuj GaggarMani SubramanianNamiki IzumiShalimarYoung-Suk LimPatrick MarcellinMaria ButiHenry L. Y. ChanKosh AgarwalNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-9 (2019) |
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Medicine R Science Q Ondrej Podlaha Edward Gane Maurizia Brunetto Scott Fung Wan-Long Chuang Calvin Q. Pan Zhaoshi Jiang Yang Liu Neeru Bhardwaj Prasenjit Mukherjee John Flaherty Anuj Gaggar Mani Subramanian Namiki Izumi Shalimar Young-Suk Lim Patrick Marcellin Maria Buti Henry L. Y. Chan Kosh Agarwal Large-scale viral genome analysis identifies novel clinical associations between hepatitis B virus and chronically infected patients |
| description |
Abstract Despite the high global prevalence of chronic hepatitis B (CHB) infection, datasets covering the whole hepatitis B viral genome from large patient cohorts are lacking, greatly limiting our understanding of the viral genetic factors involved in this deadly disease. We performed deep sequencing of viral samples from patients chronically infected with HBV to investigate the association between viral genome variation and patients’ clinical characteristics. We discovered novel viral variants strongly associated with viral load and HBeAg status. Patients with viral variants C1817T and A1838G had viral loads nearly three orders of magnitude lower than patients without those variants. These patients consequently experienced earlier viral suppression while on treatment. Furthermore, we identified novel variants that either independently or in combination with precore mutation G1896A were associated with the transition from HBeAg positive to the negative phase of infection. These observations are consistent with the hypothesis that mutation of the HBeAg open reading frame is an important factor driving CHB patient’s HBeAg status. This analysis provides a detailed picture of HBV genetic variation in the largest patient cohort to date and highlights the diversity of plausible molecular mechanisms through which viral variation affects clinical phenotype. |
| format |
article |
| author |
Ondrej Podlaha Edward Gane Maurizia Brunetto Scott Fung Wan-Long Chuang Calvin Q. Pan Zhaoshi Jiang Yang Liu Neeru Bhardwaj Prasenjit Mukherjee John Flaherty Anuj Gaggar Mani Subramanian Namiki Izumi Shalimar Young-Suk Lim Patrick Marcellin Maria Buti Henry L. Y. Chan Kosh Agarwal |
| author_facet |
Ondrej Podlaha Edward Gane Maurizia Brunetto Scott Fung Wan-Long Chuang Calvin Q. Pan Zhaoshi Jiang Yang Liu Neeru Bhardwaj Prasenjit Mukherjee John Flaherty Anuj Gaggar Mani Subramanian Namiki Izumi Shalimar Young-Suk Lim Patrick Marcellin Maria Buti Henry L. Y. Chan Kosh Agarwal |
| author_sort |
Ondrej Podlaha |
| title |
Large-scale viral genome analysis identifies novel clinical associations between hepatitis B virus and chronically infected patients |
| title_short |
Large-scale viral genome analysis identifies novel clinical associations between hepatitis B virus and chronically infected patients |
| title_full |
Large-scale viral genome analysis identifies novel clinical associations between hepatitis B virus and chronically infected patients |
| title_fullStr |
Large-scale viral genome analysis identifies novel clinical associations between hepatitis B virus and chronically infected patients |
| title_full_unstemmed |
Large-scale viral genome analysis identifies novel clinical associations between hepatitis B virus and chronically infected patients |
| title_sort |
large-scale viral genome analysis identifies novel clinical associations between hepatitis b virus and chronically infected patients |
| publisher |
Nature Portfolio |
| publishDate |
2019 |
| url |
https://doaj.org/article/8a1e909a6e354d32b320dc74b869d649 |
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