A quasi-monoclonal anti-HBs response can lead to immune escape of 'wild-type' hepatitis B virus.
Hepatitis B virus (HBV) infections can be prevented or controlled by the host humoral immune response (anti-HBs) directed against the major surface antigen (HBsAg), elicited either naturally or by vaccination. A chronic HBV carrier was found to have high levels of both virus and anti-HBs. Full-length HBV genomes were amplified from the patient's serum, sequenced and cloned. The genome was 'wild-type' HBV of genotype C and serotype adr. The sequence has remained stable, with no signs of emergence of an immune-escape mutant population. To study what was recognized by the patient's serum, viral particles were 35S-labelled and then immunoprecipitated by using the patient's serum or control sera. The patient's serum immunoprecipitated the adr HBsAg encoded by his HBV genome poorly, but efficiently recognized HBsAg of serotype ayw. When his HBV genome was modified by a point mutation to express HBsAg of serotype ayr, the patient's serum could recognize the antigen, as well as the control anti-HBs-positive serum. The patient appeared to have made a quasi-monoclonal humoral response to the y epitope. By switching to the d epitope, which requires only a point mutation, the virus could replicate, despite the high levels of anti-HBs. This study underlines the subtleties of virus-host interactions. Implications for HBV vaccination are discussed.
Margeridon
Séverine
S
INSERM U271, 151 cours A. Thomas, 69003 Lyon, France.
Lachaux
Alain
A
Department of Pediatrics, Hôpital Edouard Herriot, Lyon, France.
Trepo
Christian
C
INSERM U271, 151 cours A. Thomas, 69003 Lyon, France.
Zoulim
Fabien
F
INSERM U271, 151 cours A. Thomas, 69003 Lyon, France.
Kay
Alan
A
INSERM U271, 151 cours A. Thomas, 69003 Lyon, France.
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D002353:Carrier State / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D006509:Hepatitis B / Q000276:immunology*; D006510:Hepatitis B Antibodies / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology*; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D008969:Molecular Sequence Data; D017354:Point Mutation; D016415:Sequence Alignment
D000911:Antibodies, Monoclonal; D000939:Epitopes; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens