Sequential changes in full-length genomes of hepatitis B virus accompanying acute exacerbation of chronic hepatitis B.
OBJECTIVE
During the course of persistent hepatitis B virus infection, viral replication markedly decreases after acute exacerbation of liver inflammation accompanied by emergence of antihepatitis B e antibody (anti-HBe) and/or anti-hepatitis B surface antibody (anti-HBs). In some cases, however, persistent viral replication continues even after such exacerbation with or without HBeAg/anti-HBe seroconversion. The aim of the present study was to investigate the extent of genetic variations of HBV in this phenomenon.


METHODS
Full-length HBV genomes were amplified by polymerase chain reaction from sera of three patients before and after acute exacerbation and were directly sequenced.


RESULTS
In the whole genomes of 3215 nucleotides, only six nucleotide mutations for six amino acid substitutions (2 in the surface gene, 2 in the X gene, 1 in the core gene and 1 in the polymerase gene) were observed in patient 1, 15 mutations for 14 amino acid substitutions (1 in the pre-core codon 28, 4 in the surface gene, 4 in the core gene and 5 in the polymerase gene) were observed in patient 2, and 5 mutations for 6 amino acid substitutions (2 in the surface gene, 2 in the X gene, pre-core stop codon mutation and 1 in the polymerase gene) were observed in patient 3. Substitution in the a determinant of the surface gene, which encodes target epitopes for neutralizing antibodies, as well as those in the pre-core/core gene, which encodes epitopes for cytotoxic T cells, were mainly found.


CONCLUSIONS
HBV that remained after the emergence of anti-HBe and anti-HBs are considered to possess mutations in epitopes for both humoral and cellular immunity. These mutant HBV may be involved in the pathogenesis of persistent hepatic injury after acute exacerbation.
Asahina
Y
Y
Second Department of Internal Medicine, Faculty of Medicine, Tokyo Medical and Dental University, Japan.
Enomoto
N
N
Ogura
Y
Y
Kurosaki
M
M
Sakuma
I
I
Izumi
N
N
Marumo
F
F
Sato
C
C
D000328:Adult; D000595:Amino Acid Sequence; D002908:Chronic Disease; D018388:Codon, Terminator / Q000235:genetics; D005260:Female; D016679:Genome, Viral; D006509:Hepatitis B / Q000209:etiology* / Q000276:immunology; D006510:Hepatitis B Antibodies / Q000032:analysis; D006513:Hepatitis B e Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes / Q000737:chemistry; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000032:analysis*; D014779:Virus Replication
D018388:Codon, Terminator; D006510:Hepatitis B Antibodies; D006513:Hepatitis B e Antigens; D015345:Oligonucleotide Probes; D012367:RNA, Viral