title: Differential reactivity of putative genotype 2 hepatitis C virus F protein between chronic and recovered infections.
abstract: To date, all studies regarding hepatitis C virus (HCV) F protein have been based on expression in vitro/in vivo of recombinant protein or monoclonal antibodies derived from genotype 1a or 1b sequences, but not from other genotypes. The objective of this study was to prepare a putative genotype 2 recombinant F protein and evaluate its reactivity in plasma from individuals with chronic HCV infection or who had recovered from infection. One genotype 2 strain was selected for F protein (F-2) and core expression in bacterial culture. An ELISA was developed and applied to samples from patients with chronic infection or recovered infection of various genotypes. The anti-F-2 response in 117 samples showed a significantly higher reactivity in chronic than in recovered HCV-infected blood donors (P<0.001), but no difference was found among genotypes. However, the correlation between anti-F and anti-core was more significant in genotypes 1 and 2 than in genotype 3. Anti-F-2 titres were also significantly higher in chronic than in recovered individuals (P<0.0001). Antibody titres to recombinant genotype 2 core protein or to genotype 1 multiple proteins used in commercial anti-HCV assays paralleled the anti-F-2 end-point antibody titre. This study thus demonstrated the antigenicity of genotype 2 HCV F protein, although the exact location of the natural frameshift position remains unknown. The difference in anti-F-2 response between chronic and recovered infection, the cross-reactivity irrespective of genotype and the correlation of antibody response with structural and non-structural antigens suggest that the immune response to F protein is an integral part of the natural HCV infection.
authors.affiliation: Department of Haematology, Division of Transfusion Medicine, Cambridge Blood Centre, University of Cambridge, Long Road, Cambridge CB2 2PT, UK.
authors.forename: Wing Chia-Ming
authors.initials: WC
authors.lastname: Chuang
authors.affiliation: Department of Haematology, Division of Transfusion Medicine, Cambridge Blood Centre, University of Cambridge, Long Road, Cambridge CB2 2PT, UK.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Allain
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D005838:Genotype; D005869:Ghana; D016174:Hepacivirus / Q000145:classification / Q000235:genetics* / Q000276:immunology*; D018937:Hepatitis C Antibodies / Q000097:blood*; D019698:Hepatitis C, Chronic / Q000276:immunology* / Q000821:virology; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014758:Viral Core Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*
chemical_list: D018937:Hepatitis C Antibodies; D010455:Peptides; D011994:Recombinant Proteins; D014758:Viral Core Proteins; C433031:hepatitis C protein F, Hepatitis C virus