Novel and frequent mutations of hepatitis B virus coincide with a major histocompatibility complex class I-restricted T-cell epitope of the surface antigen.
We examined the full-length hepatitis B virus (HBV) envelope (surface antigen or HBV small surface antigen [HBsAg]) sequences of 12 different liver samples from 10 different hepatoma-containing chronic carriers. Surprisingly, novel and frequent mutations occurred predominantly at amino acids 40 and 47 of HBsAg, in addition to within a known protective B-cell epitope (so-called group a determinant of HBsAg 124-148). Approximately 58% of chronic carriers contain mutations at the group a determinant. The mutation frequency at the hotspot codons 40 and 47 is approximately 83%, 1 order of magnitude higher than at the known polymorphic sites of subtype-specific determinants at codons 122 and 160, which is approximately 4%. This new mutational domain is found to coincide with a major histocompatibility complex class I-restricted T-cell epitope. The potential biological significance of this novel mutation in the immunopathogenesis of HBV chronic carriers is discussed.
Tai
P C
PC
Department of Pathology, WHO Collaborating Center for Tropical Diseases, University of Texas Medical Branch, Galveston 77555-0609, USA.
Banik
D
D
Lin
G I
GI
Pai
S
S
Pai
K
K
Lin
M H
MH
Yuoh
G
G
Che
S
S
Hsu
S H
SH
Chen
T C
TC
Kuo
T T
TT
Lee
C S
CS
Yang
C S
CS
Shih
C
C
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000276:immunology; D006528:Carcinoma, Hepatocellular / Q000276:immunology; D002908:Chronic Disease; D018604:Epitope Mapping; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000276:immunology*; D006515:Hepatitis B virus / Q000235:genetics* / Q000254:growth & development / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D008099:Liver / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D011533:Proviruses / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*; D014779:Virus Replication
D006514:Hepatitis B Surface Antigens; D015395:Histocompatibility Antigens Class I