Conformational epitopes detected by cross-reactive antibodies to envelope 2 glycoprotein of the hepatitis C virus.
The prevalence of anti-E2 antibody in persons chronically infected with hepatitis C virus (HCV) is high irrespective of viral genotype, and this cross-reactive antibody is thought to react with a conformational epitope. To investigate the characteristics of this anti-E2 antibody, the immunoreactivity of sera from HCV-1b-infected patients was measured against various modified forms of E2 glycoprotein derived from HCV-H (genotype 1a) by an immunofluorescence technique. Twelve of 18 patients were positive for anti-E2 antibody, and 10 of the 12 required a minimal amino acid (aa) region including aa 406-644 for strong reactivity, suggesting that the major E2 antibody has a conformational epitope in this region. Subsequent analysis using mutant E2 glycoproteins designed to lose N-glycosylation potential at varying sites revealed seven important N-glycosylation sites in this region. Four of these (aa 423, 430, 448, and 576) are indispensable for an antibody response.
Nakano
I
I
Second Department of Internal Medicine, Nagoya University School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan.
Fukuda
Y
Y
Katano
Y
Y
Hayakawa
T
T
D000595:Amino Acid Sequence; D003429:Cross Reactions; D000939:Epitopes / Q000032:analysis* / Q000737:chemistry*; D005455:Fluorescent Antibody Technique; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000235:genetics / Q000276:immunology*; D018937:Hepatitis C Antibodies / Q000097:blood / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D006801:Humans; D008545:Melanoma; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology; D012680:Sensitivity and Specificity; D016415:Sequence Alignment; D014407:Tumor Cells, Cultured; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*
D000939:Epitopes; D018937:Hepatitis C Antibodies; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus