Reduced antigenicity of naturally occurring hepatitis B surface antigen variants with substitutions at the amino acid residue 126.
BACKGROUND
Substitutions at amino acid residue 126 of hepatitis B surface antigen (HBsAg) occur frequently in hepatitis B virus (HBV) isolates from patients with chronic HBV infection. These substitutions occur naturally, but their significance for viral persistence is unclear and requires further investigation.


METHODS
We amplified coding regions of HBsAg by PCR using sera from 1 patient chronically infected with HBV. Three representative clones of HBsAg with amino acid residues 126Ile (I), 126Thr (T) and 126Ser (S) were selected from sequenced clones. HBsAg 126Ala (A) mutants of subtype C/adr and D/adw were generated by site-directed mutagenesis. The HBsAg expression vectors were constructed and transiently transfected into HepG2 cells. The binding reactivity of HBsAg to anti-HBs antibodies was tested by chemiluminescent microparticle immunoassay and by immunofluorescence staining with polyclonal and monoclonal anti-HBs antibodies.


RESULTS
Diverse HBsAg variants with substitutions at amino acid residue 126 co-existed in a chronically infected HBV patient. HBsAg with the substitution 126S showed a significantly low antigenicity, while the binding reactivity to anti-HBs of other HBsAg with 126I, 126T and 126A were comparable.


CONCLUSIONS
HBsAg with the 126S substitution has a reduced antigenicity, which may contribute to immune escape in chronic HBV infection.
Qiu
Song
S
Department of Microbiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
Zhang
Jiming
J
Tian
Yongjun
Y
Yang
Yinke
Y
Huang
Hanju
H
Yang
Dongliang
D
Lu
Mengji
M
Xu
Yang
Y
D000328:Adult; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000918:Antibody Specificity; D018929:Cell Culture Techniques; D004279:DNA, Viral / Q000235:genetics; D005838:Genotype; D006509:Hepatitis B / Q000097:blood / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000737:chemistry* / Q000235:genetics* / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data
D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens