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Influence of mutations in hepatitis B virus surface protein on viral antigenicity and phenotype in occult HBV strains from blood donors.
- Source :
-
Journal of hepatology [J Hepatol] 2012 Oct; Vol. 57 (4), pp. 720-9. Date of Electronic Publication: 2012 May 23. - Publication Year :
- 2012
-
Abstract
- Background & Aims: This study aimed at investigating mutations in the hepatitis B surface protein (HBsAg) in occult hepatitis B virus (HBV) infection (OBI) and their influence on viral antigenicity and phenotype.<br />Methods: The characteristics of 61 carriers with OBI (OBI group), 153 HBsAg(+) carriers with serum HBsAg ≤ 100 IU/ml (HBsAg-L group) and 54 carriers with serum HBsAg >100 IU/ml (HBsAg-H group) from 38,499 blood donors were investigated. Mutations in the major hydrophilic region (MHR) of the viral sequences were determined. Thirteen representative MHR mutations observed in OBI sequences were antigenically characterized with a panel of monoclonal antibodies (MAbs) and commercial HBsAg immunoassays and functionally characterized in HuH7 cells and hydrodynamically injected mice.<br />Results: Of 61 OBI sequences, 34 (55.7%) harbored MHR mutations, which was significantly higher than the frequency in either the HBsAg-L (34.0%, p=0.003) or the HBsAg-H group (17.1%, p<0.001). Alterations in antigenicity induced by the 13 representative MHR mutations identified in the OBI group were assessed by reacting recombinant HBV mutants with 30 different MAbs targeting various epitopes. Four out of the 13 mutations (C124R, C124Y, K141E, and D144A) strongly decreased the analytical sensitivity of seven commercial HBsAg immunoassays, and 10 (G119R, C124Y, I126S, Q129R, S136P, C139R, T140I, K141E, D144A, and G145R) significantly impaired virion and/or S protein secretion in both HuH7 cells and mice.<br />Conclusions: MHR mutations alter antigenicity and impair virion secretion, both of which may contribute to HBsAg detection failure in individuals with OBI.<br /> (Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)
- Subjects :
- Adolescent
Adult
Animals
Antibodies, Monoclonal, Murine-Derived
Carrier State virology
Cell Line, Tumor
DNA Mutational Analysis
DNA, Viral blood
Female
Genotype
Hepatitis B virus genetics
Humans
Male
Mice
Middle Aged
Phenotype
RNA, Viral biosynthesis
Viral Envelope Proteins metabolism
Virion genetics
Virion metabolism
Young Adult
Hepatitis B Surface Antigens genetics
Hepatitis B Surface Antigens immunology
Hepatitis B virus immunology
Mutation
Viral Envelope Proteins genetics
Viral Envelope Proteins immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1600-0641
- Volume :
- 57
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of hepatology
- Publication Type :
- Academic Journal
- Accession number :
- 22634131
- Full Text :
- https://doi.org/10.1016/j.jhep.2012.05.009