title: Occult hepatitis B infection in blood donors from South East Asia: molecular characterisation and potential mechanisms of occurrence.
abstract: OBJECTIVE
  To investigate the molecular basis of occult hepatitis B virus (HBV) infection (OBI) in Asian blood donors.
  
  
  METHODS
  OBI donors from Hong Kong, Malaysia, Singapore, Taiwan and Thailand were tested for HBV serological markers, and strains were molecularly characterised.
  
  
  RESULTS
  Among 138 confirmed OBI carriers (median age 47 years), HBV genotypes B and C were dominant (60% and 34%, respectively) in agreement with the genotype distribution in chronically infected donors in the region. Viral load ranged between unquantifiable and 3670 IU/ml (median 11 IU/ml). Eleven per cent of OBIs showed an unusual anti-HBs-only serological profile without evidence of past vaccination for most of these individuals. Occult HBV strains showed a higher genetic diversity than strains from matched hepatitis B surface antigen (HBsAg)+ donors, irrespective of genotype. No unique genetic signature or evidence of reduced replication competence was found. Mutations in the vicinity of the pre-S2/S splice donor site were common in OBI(B) (44%) and OBI(C) (36%) strains. S regions from four OBI cases were transfected in HuH7 cells. Results showed limited HBsAg secretion and suggested that mutations disrupting the splice donor site structure may affect pre-S2/S mRNA splicing.
  
  
  CONCLUSIONS
  There is indirect evidence that incomplete immune control is involved in the occurrence of OBI in Asian blood donors infected with genotypes B and C as observed in Europe with genotype A2 but to a lower extent than with genotype D. A post-transcriptional mechanism may play a role in HBsAg expression in some OBIs irrespective of HBV genotype.
authors.affiliation: National Health Service Blood and Transplant, Cambridge Blood Centre, Cambridge, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Candotti
authors.forename: C Kit
authors.initials: CK
authors.lastname: Lin
authors.forename: Dalila
authors.initials: D
authors.lastname: Belkhiri
authors.forename: Tasanee
authors.initials: T
authors.lastname: Sakuldamrongpanich
authors.forename: Subhajit
authors.initials: S
authors.lastname: Biswas
authors.forename: Sujen
authors.initials: S
authors.lastname: Lin
authors.forename: Diana
authors.initials: D
authors.lastname: Teo
authors.forename: Yasmin
authors.initials: Y
authors.lastname: Ayob
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Allain
mesh_terms: D000293:Adolescent; D000328:Adult; D001210:Asia, Southeastern; D058345:Asymptomatic Infections; D015415:Biomarkers / Q000378:metabolism; D001782:Blood Donors; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D005838:Genotype; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000378:metabolism; D006515:Hepatitis B virus / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000175:diagnosis / Q000276:immunology / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012326:RNA Splicing; D060888:Real-Time Polymerase Chain Reaction; D019562:Viral Load; D055815:Young Adult
chemical_list: D015415:Biomarkers; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens