Genetic mimicry by hepatitis B virus

Abstract

THE genetic hypothesis concerning the distribution of hepatitis B antigen (HB_sAg, Australia antigen) carriers was proposed by Blumberg¹ and states that susceptibility to the chronic asymptomatic carrier state is determined by a simple autosomal recessive gene (Au¹). Persons homozygous for this gene (Au¹/Au¹) should become chronic carriers of the virus when infected with hepatitis B virus (HBV), whereas those heterozygous (Au¹/Au⁰) or negative for the susceptibility gene (Au⁰/Au⁰) should not. Asymptomatic carriers of HB_sAg are presumably chronically infected with HBV. Although independent segregation analyses of HB_sAg in the families of blood donors^2,3 and natural populations^1,4–6 have failed to reject this hypothesis, it cannot account for the occurrence of a set of identical twins in which one twin had antigen, whereas the other had antibody²; nor for children with anti-HB_s or without antigen in families where both parents were carriers of HB_sAg (refs 3, 6 and 7). Indirect support for genetic control of the outcome of HBV infection comes from studies of thalassaemic patients in Italy⁸ and asymptomatic carriers in the Solomon Islands⁹. These have suggested that susceptibility to the chronic HB_sAg carrier state may be linked to heterozygosity of Gm genes and the resulting inability to synthesise as many kinds of anti-Gm. This hypothesis has not been supported, however, by subsequent investigations of other populations^10,11. On the basis of results presented here of segregation analysis carried out on data from the Solomon Islands, we have been able to reject the existence of a susceptibility gene as a major factor leading to the HB_sAg carrier state in this population.