title: Intra-familial transmission of hepatitis B virus in Italy: phylogenetic sequence analysis and amino-acid variation of the core gene.
abstract: OBJECTIVE
  Transmission of hepatitis B virus (HBV) in countries of intermediate endemicity, such as Italy, is thought to be primarily horizontal and, to a lesser extent, vertical. Most chronic carriers therefore become infected in infancy or at a very young age. The index cases in such events have been assumed to come from within the family unit or from sources outside the immediate family, with whom the affected person is in close contact.
  
  
  METHODS
  We studied a number of Italian families with multiple members chronically infected with HBV. The precore/core region of the virus was amplified from serum derived HBV-DNA, and the sequences subjected to phylogenetic tree analysis. In addition, the extent of amino-acid variation within the core region was correlated to HLA type, determined by allele-specific PCR.
  
  
  RESULTS
  The phylogenetic tree analysis provided strong evidence of intra-familial transmission of the virus. Analysis of amino-acid substitutions in the core region in relation to HLA class II alleles from members of the same family showed that these substitutions were restricted in siblings with concordant, and more diverse in those with discordant HLA haplotypes.
  
  
  CONCLUSIONS
  This is consistent with major histocompatibility complex class II mediated selection pressure on the virus.
authors.affiliation: Department of Medicine A, Imperial College School of Medicine at St. Mary's, South Wharf Road, London W2 1NY, UK.
authors.forename: Rosa
authors.initials: R
authors.lastname: Zampino
authors.forename: Salvatore
authors.initials: S
authors.lastname: Lobello
authors.forename: Maria
authors.initials: M
authors.lastname: Chiaramonte
authors.forename: Carla
authors.initials: C
authors.lastname: Venturi-Pasini
authors.forename: Uga
authors.initials: U
authors.lastname: Dumpis
authors.forename: Mark
authors.initials: M
authors.lastname: Thursz
authors.forename: Peter
authors.initials: P
authors.lastname: Karayiannis
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D005192:Family Health; D006509:Hepatitis B / Q000635:transmission*; D006512:Hepatitis B Core Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics*; D006579:Heterozygote; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006801:Humans; D007558:Italy; D008875:Middle Aged; D008969:Molecular Sequence Data; D010802:Phylogeny; D016133:Polymerase Chain Reaction
chemical_list: D006512:Hepatitis B Core Antigens; D000949:Histocompatibility Antigens Class II