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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Santantonio
T
T
Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie, Universität Hamburg, Germany.
Jung
M C
MC
Pastore
G
G
Angarano
G
G
Günther
S
S
Will
H
H
D016000:Cluster Analysis; D004279:DNA, Viral / Q000097:blood; D005260:Female; D006509:Hepatitis B / Q000821:virology*; D006514:Hepatitis B Surface Antigens / Q000235:genetics*; D006513:Hepatitis B e Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation
D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens