Sequence analysis and functional characterization of full-length hepatitis B virus genomes from Korean cirrhotic patients with or without liver cancer

Huailiang Zhou, Dina Gewaily, Sang Hoon Ahn, Carina Preskill, Yongxiang Wang, Li Zong, Jing Zhang, Kwang Hyub Han, Jack Wands, Jisu Li, Shuping Tong

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

This study aimed to identify and characterize mutations in the hepatitis B virus (HBV) genome associated with advanced liver diseases. The 3.2-kb HBV genome of the C2 subgenotype was amplified from sera of 18 cirrhotic Korean patients with (10) or without (8) hepatocellular carcinoma (HCC), and two clones per patient were characterized by transient transfection experiments in human hepatoma cells. While A1762T/G1764A core promoter mutations were highly prevalent in both groups, the G1896A precore mutation to abolish hepatitis B e antigen (HBeAg) expression was more common in HCC clones (55% vs. 20%). High replication capacity was mostly found in HCC clones and associated with core promoter mutations, whereas more non-HCC clones harbored a nonfunctional core gene (34% vs. 8%). Large in-frame deletions in the preS region were found in 60% of HCC clones and 38% of non-HCC clones. They removed the first 11 residues of large envelope protein or impaired small envelope protein expression, or deleted a neutralizing epitope in the preS2 domain. Additional point mutations prevented middle envelope protein expression, or caused nonsense mutations in the preS or S region to truncate large and/or small envelope protein. Consequently, many clones were unable to express or secrete hepatitis B surface antigen (HBsAg). In conclusion, mutations associated with the advanced stage of chronic HBV infection are complex and diverse. Host immune pressure most likely selected for mutations in the HBV genome to abolish or reduce HBeAg or HBsAg production, to enhance genome replication, or to escape neutralizing antibodies. Some of these mutations may contribute to liver cirrhosis or HCC development.

Original languageEnglish
Pages (from-to)86-95
Number of pages10
JournalVirus Research
Volume235
DOIs
Publication statusPublished - 2017 May 2

Fingerprint

Liver Neoplasms
Hepatitis B virus
Sequence Analysis
Clone Cells
Hepatocellular Carcinoma
Genome
Mutation
Hepatitis B e Antigens
Hepatitis B Surface Antigens
Proteins
Carcinoma
Nonsense Codon
Chronic Hepatitis B
Virus Diseases
Neutralizing Antibodies
Point Mutation
Liver Cirrhosis
Transfection
Liver Diseases
Epitopes

All Science Journal Classification (ASJC) codes

  • Virology
  • Infectious Diseases
  • Cancer Research

Cite this

Zhou, Huailiang ; Gewaily, Dina ; Ahn, Sang Hoon ; Preskill, Carina ; Wang, Yongxiang ; Zong, Li ; Zhang, Jing ; Han, Kwang Hyub ; Wands, Jack ; Li, Jisu ; Tong, Shuping. / Sequence analysis and functional characterization of full-length hepatitis B virus genomes from Korean cirrhotic patients with or without liver cancer. In: Virus Research. 2017 ; Vol. 235. pp. 86-95.
@article{b5ba46c0250742b189689c64e2bb83a1,
title = "Sequence analysis and functional characterization of full-length hepatitis B virus genomes from Korean cirrhotic patients with or without liver cancer",
abstract = "This study aimed to identify and characterize mutations in the hepatitis B virus (HBV) genome associated with advanced liver diseases. The 3.2-kb HBV genome of the C2 subgenotype was amplified from sera of 18 cirrhotic Korean patients with (10) or without (8) hepatocellular carcinoma (HCC), and two clones per patient were characterized by transient transfection experiments in human hepatoma cells. While A1762T/G1764A core promoter mutations were highly prevalent in both groups, the G1896A precore mutation to abolish hepatitis B e antigen (HBeAg) expression was more common in HCC clones (55{\%} vs. 20{\%}). High replication capacity was mostly found in HCC clones and associated with core promoter mutations, whereas more non-HCC clones harbored a nonfunctional core gene (34{\%} vs. 8{\%}). Large in-frame deletions in the preS region were found in 60{\%} of HCC clones and 38{\%} of non-HCC clones. They removed the first 11 residues of large envelope protein or impaired small envelope protein expression, or deleted a neutralizing epitope in the preS2 domain. Additional point mutations prevented middle envelope protein expression, or caused nonsense mutations in the preS or S region to truncate large and/or small envelope protein. Consequently, many clones were unable to express or secrete hepatitis B surface antigen (HBsAg). In conclusion, mutations associated with the advanced stage of chronic HBV infection are complex and diverse. Host immune pressure most likely selected for mutations in the HBV genome to abolish or reduce HBeAg or HBsAg production, to enhance genome replication, or to escape neutralizing antibodies. Some of these mutations may contribute to liver cirrhosis or HCC development.",
author = "Huailiang Zhou and Dina Gewaily and Ahn, {Sang Hoon} and Carina Preskill and Yongxiang Wang and Li Zong and Jing Zhang and Han, {Kwang Hyub} and Jack Wands and Jisu Li and Shuping Tong",
year = "2017",
month = "5",
day = "2",
doi = "10.1016/j.virusres.2017.03.021",
language = "English",
volume = "235",
pages = "86--95",
journal = "Virus Research",
issn = "0168-1702",
publisher = "Elsevier",

}

Sequence analysis and functional characterization of full-length hepatitis B virus genomes from Korean cirrhotic patients with or without liver cancer. / Zhou, Huailiang; Gewaily, Dina; Ahn, Sang Hoon; Preskill, Carina; Wang, Yongxiang; Zong, Li; Zhang, Jing; Han, Kwang Hyub; Wands, Jack; Li, Jisu; Tong, Shuping.

In: Virus Research, Vol. 235, 02.05.2017, p. 86-95.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Sequence analysis and functional characterization of full-length hepatitis B virus genomes from Korean cirrhotic patients with or without liver cancer

AU - Zhou, Huailiang

AU - Gewaily, Dina

AU - Ahn, Sang Hoon

AU - Preskill, Carina

AU - Wang, Yongxiang

AU - Zong, Li

AU - Zhang, Jing

AU - Han, Kwang Hyub

AU - Wands, Jack

AU - Li, Jisu

AU - Tong, Shuping

PY - 2017/5/2

Y1 - 2017/5/2

N2 - This study aimed to identify and characterize mutations in the hepatitis B virus (HBV) genome associated with advanced liver diseases. The 3.2-kb HBV genome of the C2 subgenotype was amplified from sera of 18 cirrhotic Korean patients with (10) or without (8) hepatocellular carcinoma (HCC), and two clones per patient were characterized by transient transfection experiments in human hepatoma cells. While A1762T/G1764A core promoter mutations were highly prevalent in both groups, the G1896A precore mutation to abolish hepatitis B e antigen (HBeAg) expression was more common in HCC clones (55% vs. 20%). High replication capacity was mostly found in HCC clones and associated with core promoter mutations, whereas more non-HCC clones harbored a nonfunctional core gene (34% vs. 8%). Large in-frame deletions in the preS region were found in 60% of HCC clones and 38% of non-HCC clones. They removed the first 11 residues of large envelope protein or impaired small envelope protein expression, or deleted a neutralizing epitope in the preS2 domain. Additional point mutations prevented middle envelope protein expression, or caused nonsense mutations in the preS or S region to truncate large and/or small envelope protein. Consequently, many clones were unable to express or secrete hepatitis B surface antigen (HBsAg). In conclusion, mutations associated with the advanced stage of chronic HBV infection are complex and diverse. Host immune pressure most likely selected for mutations in the HBV genome to abolish or reduce HBeAg or HBsAg production, to enhance genome replication, or to escape neutralizing antibodies. Some of these mutations may contribute to liver cirrhosis or HCC development.

AB - This study aimed to identify and characterize mutations in the hepatitis B virus (HBV) genome associated with advanced liver diseases. The 3.2-kb HBV genome of the C2 subgenotype was amplified from sera of 18 cirrhotic Korean patients with (10) or without (8) hepatocellular carcinoma (HCC), and two clones per patient were characterized by transient transfection experiments in human hepatoma cells. While A1762T/G1764A core promoter mutations were highly prevalent in both groups, the G1896A precore mutation to abolish hepatitis B e antigen (HBeAg) expression was more common in HCC clones (55% vs. 20%). High replication capacity was mostly found in HCC clones and associated with core promoter mutations, whereas more non-HCC clones harbored a nonfunctional core gene (34% vs. 8%). Large in-frame deletions in the preS region were found in 60% of HCC clones and 38% of non-HCC clones. They removed the first 11 residues of large envelope protein or impaired small envelope protein expression, or deleted a neutralizing epitope in the preS2 domain. Additional point mutations prevented middle envelope protein expression, or caused nonsense mutations in the preS or S region to truncate large and/or small envelope protein. Consequently, many clones were unable to express or secrete hepatitis B surface antigen (HBsAg). In conclusion, mutations associated with the advanced stage of chronic HBV infection are complex and diverse. Host immune pressure most likely selected for mutations in the HBV genome to abolish or reduce HBeAg or HBsAg production, to enhance genome replication, or to escape neutralizing antibodies. Some of these mutations may contribute to liver cirrhosis or HCC development.

UR - http://www.scopus.com/inward/record.url?scp=85018659902&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85018659902&partnerID=8YFLogxK

U2 - 10.1016/j.virusres.2017.03.021

DO - 10.1016/j.virusres.2017.03.021

M3 - Article

C2 - 28373061

AN - SCOPUS:85018659902

VL - 235

SP - 86

EP - 95

JO - Virus Research

JF - Virus Research

SN - 0168-1702

ER -