Characterization of occult hepatitis B virus from blood donors carrying genotype A2 or genotype D strains.
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.
Candotti
Daniel
D
National Health Service Blood and Transplant, Cambridge Blood Centre, Cambridge, UK.
Grabarczyk
Piotr
P
Ghiazza
Paola
P
Roig
Roberto
R
Casamitjana
Natalia
N
Iudicone
Paola
P
Schmidt
Michael
M
Bird
Arthur
A
Crookes
Robert
R
Brojer
Ewa
E
Miceli
Michelina
M
Amiri
Azin
A
Li
Chengyao
C
Allain
Jean-Pierre
JP
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
D004279:DNA, Viral; D000939:Epitopes; D014759:Viral Envelope Proteins