Familial clustering of HBV pre-C and pre-S mutants

Little is known about the persistence and risk of infection with hepatitis B viruses (HBV) containing mutations in the pre-C and pre-S region. The aim of this study was to study the long-term persistence and the risk of intrafamilial spreading of these variants.

Serological markers were analyzed immunologically and pre-C and pre-S sequences of HBV DNA in sera from several members of five families by DNA amplification and direct sequencing.

In most HBV-DNA positive individuals of each family, either the dominant HBV population or a subpopulation had a stop codon in the pre-C region which prevented expression of e-antigen. The pre-S region of the dominant virus populations of 8/15 HBV-DNA positive sera showed different deletions or a pre-S2 translation initiation codon mutation in addition to various point mutations. Selection for pre-C and pre-S mutant viruses from a predominant "wildtype" virus population was observed in three individuals during the natural course of infection. Persistence of a pre-C/pre-S double mutant virus as a stable strain for 6 years was found in one patient.

These data indicate extensive intrafamilial clustering of HBV variants with mutations in the pre-C and pre-S regions due to patient-specific selection mechanisms and long-term persistence of some mutants as stable strains. The type of viruses found suggests that occasionally virus subpopulations are selectively transmitted or become a dominant virus population after selection.