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eISSN: 1643-3750

Analysis of HBs antigen negative variant of hepatitis B virus: unique substitutions,Glu129 to Asp and Gly145 to Ala in the surface antigen gene.

H Nawata, M Mukaide, T Kumazawa, H Iwamoto, M Enjoji, T Koyanagi, K Koto, R Sugimoto, H Sakai, M Nakamuta

Med Sci Monit 2000; 6(6): CS1165-1169

ID: 421207

Published:


We analyzed the surface gene (S gene) of a hepatitis B virus (HBV) isolatewith mutations of envelope protein that rendered it undetectable by both a monoclonal hepatitis B surfaceantigen (HBsAg) enzyme-linked immunosorbent assay (ELISA) and polyclonal HBsAg radioimmunoassay (RIA).Sequencing of independently cloned products of HBV polymerase chain reaction revealed several point mutationswithin the S gene. Rare substitution was identified both at positions 129 (glutamine to asparagine) andat position 145 (glycine to alanine) in the 'a' determinant region, which is considered to be withina larger antigenic area known as the major hydrophilic region (MHR). A computer-assisted analysis ofprotein secondary structure could not find any significant difference between this mutant and wild-typeHBsAg. However, the substitution of substitution glycine to alanine at position 129 introduce a putativeglycosylation site (Asn-Gly-Thr), which may interfere with the antigenicity of HbsAg. Also, HBV variantwith substitution at position 145 (Gly to Ala) has been recently reported to be antigenically alteredand to show impaired recognition by polyclonal hepatitis B hyperimmune globulin in vitro. These geneticmutations in the S gene inside MHR may allow to escape detection by standard HBsAg assays.

Keywords: Amino Acid Sequence, Amino Acid Substitution, Epitopes, False Negative Reactions, Genes, Viral, Glycosylation, Hepatitis B Surface Antigens, Hepatitis B virus, Hepatitis B, Chronic, Humans, Male, Middle Aged, Molecular Sequence Data, Point Mutation, Protein Structure, Secondary, Variation (Genetics)



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