Chapter 14 - In vitro phenotype of HBV variants in patients with fulminant hepatitis B

Abstract

Both viral factors and the host's immune response may play an important role in the pathogenesis of fulminant hepatitis B infections. The aim of the study described in this chapter was to functionally characterize hepatitis B virus (HBV) strains isolated from patients with fulminant hepatitis B (FHB). In the study, phenotypes of the viral mutants isolated from patients with FHB were investigated by transfection studies in human hepatoma cells. One of eight patients with FHB was infected with high-replicating viral variants. HBV mutants with a severe secretion defect were found in a mixed population in two patients investigated. Polymerase chain reaction (PCR) products were directly transfected to investigate the phenotype of the dominant viral population of the respective patient. These data show that a high-replicating or secretion-defective phenotype of the viral variants is not a general characteristic for patients with FHB but may in some cases contribute to the disease pathogenesis. Subsequent construction and functional analysis of viral hybrid genomes, in which parts of the mutant viruses were introduced into wildtype virus, allowed determination of the sequence changes responsible for the specific viral phenotype.