title: T cell responses and viral variability in blood donation candidates with occult hepatitis B infection.
abstract: OBJECTIVE
  Occult HBV infection (OBI) is defined by the presence of HBV DNA in the liver and/or serum and negative HBsAg testing. Since the implementation of highly sensitive HBV DNA screening, OBI is also detected in healthy blood donors. The aims of this study were to investigate HBV-specific immune responses and genetic variability in donors with OBI, established by HBV DNA in serum.
  
  
  METHODS
  HBV-specific T-cell responses to HBV antigens were tested in 34 OBI donors by IFN-γ ELISpot, cytometric bead array, and intracellular cytokine staining. As comparison populations, 36 inactive HBV carriers, 22 donors with spontaneously resolved HBV infection, 24 vaccinated donors, and 25 seronegative donors were also included. Surface, pre-S, and pre-c/core genes from 44 genotype D isolates (24 OBI and 20 HBsAg-positive) were sequenced.
  
  
  RESULTS
  The immune response of OBI donors to the 3 HBV antigens was 29-41%, similar to the response in subjects with resolved HBV infection and higher than that in HBsAg-positive subjects. On sequence analysis, OBI donors presented a higher HBsAg mutation rate than HBsAg-positive subjects. Mutations were clustered in the major hydrophilic region of HBsAg, and no stop codons or relevant mutations that could affect antigen formation or detection were observed.
  
  
  CONCLUSIONS
  Our results suggest that immune response can suppress viral replication to low levels and HBsAg expression to undetectable levels in OBI blood donors. Relevant mutations were not found in the genomic HBsAg coding region. Hence, the fact that HBsAg was not detected in OBI is likely due to low HBsAg production, rather than to a failure of laboratory reagents.
authors.affiliation: Banc de Sang i Teixits, Institut Català de la Salut, Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Bes
authors.forename: Victor
authors.initials: V
authors.lastname: Vargas
authors.forename: Maria
authors.initials: M
authors.lastname: Piron
authors.forename: Natalia
authors.initials: N
authors.lastname: Casamitjana
authors.forename: Juan Ignacio
authors.initials: JI
authors.lastname: Esteban
authors.forename: Nuria
authors.initials: N
authors.lastname: Vilanova
authors.forename: Asuncion
authors.initials: A
authors.lastname: Pinacho
authors.forename: Josep
authors.initials: J
authors.lastname: Quer
authors.forename: Lluis
authors.initials: L
authors.lastname: Puig
authors.forename: Jaime
authors.initials: J
authors.lastname: Guardia
authors.forename: Silvia
authors.initials: S
authors.lastname: Sauleda
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D000956:Antigens, Viral / Q000276:immunology; D001782:Blood Donors; D016207:Cytokines / Q000378:metabolism; D004279:DNA, Viral / Q000097:blood*; D005260:Female; D016679:Genome, Viral / Q000235:genetics; D006509:Hepatitis B / Q000097:blood* / Q000453:epidemiology / Q000276:immunology*; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D015995:Prevalence; D012189:Retrospective Studies; D013601:T-Lymphocytes / Q000276:immunology*; D055815:Young Adult
chemical_list: D000956:Antigens, Viral; D016207:Cytokines; D004279:DNA, Viral