Viral Mutants and Fulminant Hepatitis. A Dominant Hepatitis B Virus Population Defective in Virus Secretion Because of Several S-Gene Mutations from a Patient with Fulminant Hepatitis

Abstract

Summary : Kalinina et al. isolated variants of hepatitis B virus (HBV) with enhanced replication competence and a possible defect in viral particle secretion from a patient with fulminant recurrent HBV infection after liver transplantation. Both viral features may have contributed to the severity of the disease. The aim of this study was to prove the secretion defect of these variants, to analyze the consequences, and to identify the responsible viral mutations. The variant genomes and ap- propriate wild-type variant hybrid genomes were characterized functionally after transfection in human hepatoma cells. Two cloned genomes and the polymerase chain reaction-amplified mixture of full- length genomes showed a block in viral particle secretion. A combination of amino acid changes in the S protein caused this block, including the mutation G145R, frequently emerging after hyperimmunoglobulin treatment. The mutations induced retention of the surface proteins in an endoplasmic reticulum-like compartment, but did not induce intracellular accumulation. The authors concluded that a dominant HBV population with a severe defect in viral particle secretion caused by mutations in the S-gene in combination with the enhanced replication competence might have contributed to the fulminant clinical course of the infection.