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Neonatal fulminant hepatitis B: structural and functional analysis of complete hepatitis B virus genomes from mother
M Sterneck1, T Kalinina, S Otto
1Department of Medicine, Surgery, and Pediatrics, University Hospital Eppendorf, Hamburg, Germany. sterneck@uke.uni-hamburg.de
Insights
No specific hepatitis B virus (HBV) strain caused fulminant hepatitis B (FHB) in newborns. Instead, de novo infections with HBV variants defective in HBe antigen and pre-S2 protein synthesis likely contributed to severe disease.
Area of Science:
- Virology
- Hepatology
- Genetics
Background:
- Hepatitis B virus (HBV) transmission from carrier mothers to infants can cause neonatal fulminant hepatitis B (FHB).
- Investigating specific HBV variants selected during mother-to-infant transmission is crucial for understanding FHB pathogenesis.
Observation:
- Full-length HBV genomes from a mother-infant pair with neonatal FHB were sequenced.
- The dominant maternal and neonatal HBV populations exhibited high genetic similarity (99.8%).
- Identified mutations included a precore stop codon, core promoter substitutions (T-1762, A-1764), and pre-S2 start codon mutations.
Findings:
- Transfection studies showed no significant increase in HBV DNA particle synthesis or release by maternal/neonatal variants compared to wild-type.
- No distinct HBV strain was selected during the transmission leading to neonatal FHB.
- The study suggests de novo infection with HBV variants possessing defects in HBe antigen and pre-S2 protein synthesis, rather than high replication competence, contributed to the severe disease course.
Implications:
- These findings challenge the hypothesis of a specific, highly virulent HBV strain driving neonatal FHB.
- Understanding the role of defective viral variants in FHB pathogenesis may inform future therapeutic strategies.
- Further research into the functional impact of these mutations on viral replication and disease severity is warranted.
Abstract:
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.