title: Characterization of occult hepatitis B virus from blood donors carrying genotype A2 or genotype D strains.
abstract: OBJECTIVE
  Nucleic acid testing (NAT) for hepatitis B virus (HBV) DNA in blood donations identified occult HBV infection (OBI) as a potential threat to blood safety.
  
  
  METHODS
  A collaborative study was undertaken to explore the molecular basis of OBIs prevalent in Europe in relation to clinical and serological data.
  
  
  RESULTS
  Ninety-one percent of 77 donor samples of European origin HBV DNA positive but HBV surface antigen (HBsAg) negative were confirmed. Viral load ranged between unquantifiable and 5640 IU/mL (median 25 IU/mL). Fifty-two strains were genotyped (14 HBV(A2) and 38 HBV(D)). Compared to HBsAg+ samples, genotype D was significantly more frequent than genotype A2 in OBIs from Poland or Italy (P<0.04). Amino acid substitutions were concentrated in the immunologically active parts of the Pre-S/S proteins (P<0.0001) affecting both cellular CD8 T-cell epitopes and B-cell neutralizing Major Hydrophilic Region epitopes. Substitutions were more frequent in OBIs than in HBsAg+ strains of both genotype D (P<0.001) and A2 (P<0.01), in OBIs of genotype D than A2 in the 'a' region (P<0.001) but not cellular epitopes, and in anti-HBs+ than anti-HBs- OBIs (P<0.001).
  
  
  CONCLUSIONS
  Results support the hypothesis that humoral and cellular immune pressure on the HBV envelope proteins are major mechanisms generating OBI.
authors.affiliation: National Health Service Blood and Transplant, Cambridge Blood Centre, Cambridge, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Candotti
authors.forename: Piotr
authors.initials: P
authors.lastname: Grabarczyk
authors.forename: Paola
authors.initials: P
authors.lastname: Ghiazza
authors.forename: Roberto
authors.initials: R
authors.lastname: Roig
authors.forename: Natalia
authors.initials: N
authors.lastname: Casamitjana
authors.forename: Paola
authors.initials: P
authors.lastname: Iudicone
authors.forename: Michael
authors.initials: M
authors.lastname: Schmidt
authors.forename: Arthur
authors.initials: A
authors.lastname: Bird
authors.forename: Robert
authors.initials: R
authors.lastname: Crookes
authors.forename: Ewa
authors.initials: E
authors.lastname: Brojer
authors.forename: Michelina
authors.initials: M
authors.lastname: Miceli
authors.forename: Azin
authors.initials: A
authors.lastname: Amiri
authors.forename: Chengyao
authors.initials: C
authors.lastname: Li
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Allain
mesh_terms: D000328:Adult; D000368:Aged; D001782:Blood Donors; D004279:DNA, Viral / Q000235:genetics*; D000939:Epitopes / Q000235:genetics; D005060:Europe; D005260:Female; D005838:Genotype; D006509:Hepatitis B / Q000097:blood* / Q000175:diagnosis / Q000208:ethnology; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D014759:Viral Envelope Proteins / Q000235:genetics
chemical_list: D004279:DNA, Viral; D000939:Epitopes; D014759:Viral Envelope Proteins