title: The genetic backbone modulates the phenotype of hepatitis B surface antigen mutants.
abstract: Hepatitis B virus (HBV) vaccine and diagnostic escape mutants are a growing concern. The principle target of detection, hepatitis B surface antigen (HBsAg), encoded by S, is completely overlapped by the reverse transcriptase encoding P. With the increased incidence of nucleos(t)ide analogue resistance altering P, the concurrent impact on S must be assessed. HBV DNA from 59 HBsAg-positive plasma samples was sequenced across the polymerase/surface region and the amino acid sequence of HBsAg was inferred. ELISAs were formatted containing individually bound monoclonal antibodies directed against three discrete epitopes on HBsAg. Similar point mutations occurring in different genotypes were shown to influence epitope conformation differently, indicating that the genetic backbone is a major factor in predicting phenotype. C-terminal changes associated with antiviral resistance were found to modulate epitope profiles of HBsAg. Treatment options which may promote drug resistance should be avoided to both protect antiviral treatment and prevent facilitation of vaccine and diagnostic escape mutants.
authors.affiliation: Blood Borne Virus Unit, Virus Reference Department, Centre for Infections, Health Protection Agency, London, UK.
authors.forename: Mathew A
authors.initials: MA
authors.lastname: Beale
authors.forename: Samreen
authors.initials: S
authors.lastname: Ijaz
authors.forename: Richard S
authors.initials: RS
authors.lastname: Tedder
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D024882:Drug Resistance, Viral; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D006509:Hepatitis B / Q000821:virology; D006510:Hepatitis B Antibodies / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000235:genetics* / Q000276:immunology*; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D017422:Sequence Analysis, DNA
chemical_list: D000911:Antibodies, Monoclonal; D004279:DNA, Viral; D000939:Epitopes; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens