Impact of Nucleotide Mutations at the HNF3- and HNF4-Binding Sites in Enhancer 1 on Viral Replication in Patients with Chronic Hepatitis B Virus Infection.

Content Provider	Europe PMC
Author	Cho, Eun-young Kim, Hyung-jin Park, Channy So, Hong-seob Park, Rae Kil Kim, Haak Cheoul
Copyright Year	2013
Abstract	Background/AimsThe hepatitis B virus (HBV) genome contains binding sites for hepatocyte nuclear factors (HNF) 3 and 4 in the core domain of enhancer 1 (Enh1), and mutations in this domain have a strong impact on virus replication. We aimed to identify frequent base-mutation sites in the core domain of Enh1 and to examine the impact of these mutations on viral replication.MethodsWe studied virological characteristics and genetic sequences in 387 patients with chronic hepatitis B. We evaluated functional differences associated with specific mutations within the core domain of Enh1.ResultsMutations in the core domain were found with significant frequency in C1126 (122/387 [31.5%], the binding site for HNF3) and in C1134 (106/387 [27.4%], the binding site for HNF4). A single mutation at nt 1126 (C1126) was identified in 17/123 (13.8%), and 105/123 (85.4%) had double mutations (C1126/1134). The level of HBV DNA (log10 copies/mL) was lower in single mutants (C1126, 5.81±1.25) than in wild (6.80±1.65) and double mutants (C1126/1134, 6.81±1.54). Similarly, the relative luciferase activity of C1126 and C1126/C1134 was 0.18 and 1.12 times that of the wild-type virus, respectively.ConclusionsMutations in the HNF3 binding site inhibit viral replication, whereas mutations at the HNF4 binding site restore viral replication.
ISSN	19762283
Journal	Gut and Liver
Volume Number	7
PubMed Central reference number	PMC3782672
Issue Number	5
PubMed reference number	24073315
e-ISSN	20051212
DOI	10.5009/gnl.2013.7.5.569
Language	English
Publisher	the Korean Association for the Study of the Liver Korean Association for the Study of Intestinal Diseases Korean Society of Gastrointestinal Cancer Korean Pancreatobiliary Association the Korean Society of Neurogastroenterology and Motility Korean College of Helicobacter and Upper Gastrointestinal Research The Korean Society of Gastroenterology the Korean Society of Gastrointestinal Endoscopy
Publisher Date	2013-06-11
Access Restriction	Open
Rights License	This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright © 2013 by the Korean Society of Gastroenterology, the Korean Society of Gastrointestinal Endoscopy, the Korean Society of Neurogastroenterology and Motility, Korean College of Helicobacter and Upper Gastrointestinal Research, Korean Association for the Study of Intestinal Diseases, the Korean Association for the Study of the Liver, Korean Pancreatobiliary Association, and Korean Society of Gastrointestinal Cancer
Subject Keyword	Hepatocyte nuclear factors Hepatitis B virus Virus replication
Content Type	Text
Resource Type	Article
Subject	Hepatology Gastroenterology