大规模病毒基因组分析确定了乙型肝炎病毒和慢性感染患者

StephenW

Sci Rep. 2019 Jul 19;9(1):10529. doi: 10.1038/s41598-019-46609-7.
Large-scale viral genome analysis identifies novel clinical associations between hepatitis B virus and chronically infected patients.
Podlaha O1, Gane E2, Brunetto M3,4, Fung S5, Chuang WL6, Pan CQ7, Jiang Z8, Liu Y8, Bhardwaj N8, Mukherjee P8, Flaherty J8, Gaggar A8, Subramanian M8, Izumi N9, Shalimar10, Lim YS11, Marcellin P12, Buti M13, Chan HLY14, Agarwal K15.
Author information

1
    Gilead Sciences Inc., 333 Lakeside Drive, Foster City, CA, 94404, USA. [email protected].
2
    Auckland Clinical Studies, Auckland, New Zealand.
3
    Internal Medicine, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
4
    Liver Unit, University Hospital of Pisa Hepatology Unit, University Hospital of Pisa, Pisa, Italy.
5
    Toronto General Hospital, Toronto, ON, Canada.
6
    Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
7
    Division of Gastroenterology and Hepatology, Department of Medicine, NYU Langone Health, NYU School of Medicine, New York, NY, USA.
8
    Gilead Sciences Inc., 333 Lakeside Drive, Foster City, CA, 94404, USA.
9
    Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
10
    All India Institute of Medical Sciences, Department of Gastroenterology, New Delhi, India.
11
    Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
12
    Service d'Hépatologie, Hôpital Beaujon, Clichy, France.
13
    Liver Unit, Department of Medicine, Hospital General Universitari Vall d'Hebron and Ciberehd del Instituto Carlos III, Barcelona, Spain.
14
    The Chinese University of Hong Kong, Hong Kong, China.
15
    Kings College Hospital, London, UK.

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.

PMID:
    31324819
DOI:
    10.1038/s41598-019-46609-7

StephenW

SciRep.2019年7月19日; 9（1）：10529。 doi：10.1038 / s41598-019-46609-7。
大规模病毒基因组分析确定了乙型肝炎病毒和慢性感染患者之间的新型临床关联。
Podlaha O1，Gane E2，Brunetto M3,4，Fung S5，Chuang WL6，Pan CQ7，Jiang Z8，Liu Y8，Bhardwaj N8，Mukherjee P8，Flaherty J8，Gaggar A8，Subramanian M8，Izumi N9，Shalimar10，Lim YS11，Marcellin P12，Buti M13，Chan HLY14，Agarwal K15。
作者信息

1
Gilead Sciences Inc.，333 Lakeside Drive，Foster City，CA，94404，USA。 [email protected]。
2
奥克兰临床研究，新西兰奥克兰。
3
内科，意大利比萨比萨大学临床和实验医学系。
4
意大利比萨大学医院比萨大学医院肝病科肝脏科。
五
多伦多综合医院，多伦多，ON，加拿大。
6
台湾高雄市高雄医科大学高雄医科大学附属医院。
7
纽约大学医学系消化内科和肝脏病学系，纽约大学医学院Langone Health，纽约，纽约，美国。
8
Gilead Sciences Inc.，333 Lakeside Drive，Foster City，CA，94404，USA。
9
日本东京武藏野红十字医院消化内科和肝病学系。
10
全印度医学科学研究所，印度新德里消化内科。
11
韩国首尔蔚山大学医学院牙山医学系消化内科
12
Service d'Hépatologie，HôpitalBeaujon，Clichy，France。
13
西班牙巴塞罗那Vall d'Hebron大学医学系和Ciberehd del Instituto Carlos III医学系肝脏科。
14
香港中文大学，中国香港。
15
英国伦敦国王学院医院。

抽象

尽管慢性乙型肝炎（CHB）感染的全球流行率很高，但缺乏覆盖大型患者队列的整个乙型肝炎病毒基因组的数据集，这极大地限制了我们对这种致命疾病中涉及的病毒遗传因素的理解。我们对慢性HBV感染患者的病毒样本进行了深度测序，以研究病毒基因组变异与患者临床特征之间的关系。我们发现了与病毒载量和HBeAg状态密切相关的新型病毒变种。具有病毒变体C1817T和A1838G的患者具有接近三个数量级的病毒载量，而不具有那些变体的患者。此外，我们鉴定了独立或与前核心突变G1896A组合的新变体与HBeAg阳性转变为感染阴性期相关。观察结果e-。病毒变异影响临床表型。

结论：
31324819
DOI：
10.1038 / s41598-019-46609-7

StephenW

https://www.nature.com/articles/s41598-019-46609-7.pdf