CTL escape mutations of core protein are more frequent in strains of HBeAg negative patients with low levels of HBV DNA.
BACKGROUND
Recent studies have suggested that Cytotoxic T lymphocytes (CTL) play a key role in eliminating hepatitis B virus (HBV).


OBJECTIVE
We aimed to investigate the role of mutations in different immune epitopes of hepatitis B core antigen (HBcAg) among Iranians with hepatitis B e antigen negative chronic hepatitis B (e-CHB), and asymptomatic carriers (ASCs).


METHODS
Amino acids 1-150 of HBcAg were characterized for HBV strains from 29 e-CHB patients and 48 ASCs from Iran. All patients were infected with HBV genotype D and had previously been investigated for the presence of pre-core and basic core promoter (BCP) mutants.


RESULTS
Amino acid mutations of core protein were observed more frequently in HBV strains from ASCs than e-CHB patients (p=0.014). Asn(67) mutation was mutually exclusive to the combination Ile(66) and Ser(69) (P<0.001). Substitutions for Ser(21) and Thr12Ser were associated with lower serum levels of HBV DNA (p<0.001). None of the patients with mutations in HLA-A2 CTL epitope, 18-27, had serum HBV DNA more than 10(5)copies/mL (p<0.001). By multivariate analysis, high level (>10(5)copies/mL) of serum HBV DNA was inversely associated with the presence of mutations in CTL epitopes of HBc (OR: 0.11, p=0.015), while it was directly associated with the presence of promoter double T(1762)A(1764) mutations together with G(1757) (OR: 16.87, p=0.004).


CONCLUSIONS
The inverse correlation between serum levels of HBV DNA and CTL escape mutations of the core protein in HBeAg seroconverted patients, supports the notion that selection of CTL escape mutations consolidates the persistence of HBV infection despite reducing viral fitness.
Sendi
Hossein
H
Department of Virology, Swedish Institute for Infectious Disease Control, SE-171 82 Solna, Sweden. hsendi@uncc.edu
Mehrab-Mohseni
Marjan
M
Shahraz
Saeid
S
Norder
Helene
H
Alavian
Seyed-Moayed
SM
Noorinayer
Babak
B
Zali
Mohammad R
MR
Pumpens
Paul
P
Bonkovsky
Herbert L
HL
Magnius
Lars O
LO
D000595:Amino Acid Sequence; D002353:Carrier State / Q000821:virology; D016009:Chi-Square Distribution; D004279:DNA, Viral / Q000097:blood; D000939:Epitopes / Q000235:genetics; D006509:Hepatitis B / Q000097:blood / Q000276:immunology* / Q000821:virology; D006512:Hepatitis B Core Antigens / Q000235:genetics* / Q000276:immunology; D006513:Hepatitis B e Antigens / Q000235:genetics* / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics* / Q000472:pathogenicity; D006801:Humans; D016015:Logistic Models; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015999:Multivariate Analysis; D009154:Mutation; D016415:Sequence Alignment; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D004279:DNA, Viral; D000939:Epitopes; D006512:Hepatitis B Core Antigens; D006513:Hepatitis B e Antigens