NEONATAL FULMINANT-HEPATITIS-B - STRUCTURAL AND FUNCTIONAL-ANALYSIS OF COMPLETE HEPATITIS-B VIRUS GENOMES FROM MOTHER AND INFANT

Transmission of hepatitis B virus (HBV) from anti-hepatitis B e (anti- HBe)-positive carrier mothers to their infants mag. result in neonatal fulminant hepatitis B (FHB), We investigated whether HBV variants wit h a particular DNA sequence and functional phenotype, responsible for FHB, are selected during transmission. Full-length HBV genomes from a mother-infant pair were completely sequenced and transfected into huma n hepatoma cells. The dominant neonatal and maternal HBV populations w ere nearly identical (homology 99.8%) and showed a precore stop codon mutation, T-1762 and A-1764 substitutions in the core promoter region, and pre-S2 start codon mutations. Cells transfected with variants fro m mother and child, compared with wild-type virus, synthesized and rel eased a similar number or fewer HBV DNA-containing particles. In concl usion, no particular HBV strain emerged during neonatal FHB. In this c ase, a de novo infection with variants showing a defect in HBe antigen and pre-S2 protein synthesis but not a high replication competence pr obably contributed to the fulminant disease course.