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 may result in neonatal fulminant hepatitis B (FHB). We investigated whether HBV variants with 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 human hepatoma cells. The dominant neonatal and maternal HBV populations were 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 from mother and child, compared with wild-type virus, synthesized and released a similar number or fewer HBV DNA-containing particles. In conclusion, no particular HBV strain emerged during neonatal FHB. In this case, a de novo infection with variants showing a defect in HBe antigen and pre-S2 protein synthesis but not a high replication competence probably contributed to the fulminant disease course.
Sterneck
M
M
Department of Medicine, Surgery, and Pediatrics, University Hospital Eppendorf, Hamburg, Germany. sterneck@uke.uni-hamburg.de
Kalinina
T
T
Otto
S
S
Günther
S
S
Fischer
L
L
Burdelski
M
M
Greten
H
H
Broelsch
C E
CE
Will
H
H
D000328:Adult; D001483:Base Sequence; D004279:DNA, Viral / Q000097:blood; D005260:Female; D014644:Genetic Variation; D016679:Genome, Viral; D006509:Hepatitis B / Q000635:transmission / Q000821:virology*; D006515:Hepatitis B virus / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000821:virology*; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D014779:Virus Replication
D004279:DNA, Viral