Detection and significance of a G1862T variant of hepatitis B virus in Chinese patients with fulminant hepatitis.
The prevalence of a G1862T variant of hepatitis B virus (HBV) has been investigated in patients with fulminant hepatitis and chronic liver disease, using primer mismatch amplification, followed by restriction fragment length polymorphism analysis. This variant was five times more common in patients with fulminant hepatitis (13.7%, 7 of 52) than in chronic carriers (2.5%, 2 of 81). The G-->T substitution at position 1862 leads to an amino acid change in codon 17 of the precore protein of the virus, which is part of a signal peptidase recognition motif. Variants with this mutation were only seen in patients infected with genotype B. In vitro translation experiments showed that this variant has greatly reduced capacity to produce hepatitis B e antigen (HBeAg) from its precore protein precursor. Furthermore, 88.5% of patients with fulminant hepatitis had mutations that are known to be associated with abrogated or reduced production of HBeAg. This suggests that, following HBV infection, the absence or reduced amounts of HBeAg may be a contributing factor in fulminant disease.
Hou
Jinlin
J
Department of Medicine A, Imperial College of Science, Technology and Medicine, St Mary's Campus, South Wharf Road, London W2 1NY, UK2.|Department of Infectious Diseases, Nanfang Hospital, The First Medical College of PLA, Guangzhou 510515, China1.
Lin
Yulong
Y
Department of Infectious Diseases, Nanfang Hospital, The First Medical College of PLA, Guangzhou 510515, China1.
Waters
Jenny
J
Department of Medicine A, Imperial College of Science, Technology and Medicine, St Mary's Campus, South Wharf Road, London W2 1NY, UK2.
Wang
Zhanhui
Z
Department of Infectious Diseases, Nanfang Hospital, The First Medical College of PLA, Guangzhou 510515, China1.
Min
Jia
J
You'an Hospital for Infectious Diseases, Beijing, China3.
Liao
Huiyu
H
You'an Hospital for Infectious Diseases, Beijing, China3.
Jiang
Jiaji
J
Fuzhou Hospital for Infectious Diseases, Fuzhou, China4.
Chen
Jinjun
J
Department of Infectious Diseases, Nanfang Hospital, The First Medical College of PLA, Guangzhou 510515, China1.
Luo
Kangxian
K
Department of Infectious Diseases, Nanfang Hospital, The First Medical College of PLA, Guangzhou 510515, China1.
Karayiannis
Peter
P
Department of Medicine A, Imperial College of Science, Technology and Medicine, St Mary's Campus, South Wharf Road, London W2 1NY, UK2.
D000328:Adult; D019943:Amino Acid Substitution; D002460:Cell Line; D002681:China; D005260:Female; D005838:Genotype; D006509:Hepatitis B / Q000175:diagnosis / Q000821:virology*; D006513:Hepatitis B e Antigens / Q000032:analysis / Q000096:biosynthesis; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D011498:Protein Precursors / Q000032:analysis / Q000096:biosynthesis; D016415:Sequence Alignment; D014162:Transfection; D014759:Viral Envelope Proteins / Q000032:analysis / Q000096:biosynthesis
D006513:Hepatitis B e Antigens; D011498:Protein Precursors; D014759:Viral Envelope Proteins