Molecular characterization of a new variant of hepatitis B virus in a persistently infected homosexual man.
Based on the diversity of nucleotide sequences of cloned hepatitis B virus DNA genomes, we have predicted possible replication of genetic variants of human hepatitis B virus. This prediction is exemplified by studies of a chronic carrier of HBsAg/adw2, who lacked anti-HBc but carried exceedingly high levels of hepatitis B virus DNA in serum. Molecular characterization of a number of clones revealed a restriction map that deviated significantly from the typical pattern of the adw2 subtype, especially around the EcoRI site commonly used as a reference point. Mutations appearing consistently in the precore and core regions included (a) mutation in the precore region resulting in a termination codon after the initiation codon, (b) mutation of the core initiation codon and (c) an inframe insert of 36 nucleotides in the precore region with a new initiation site for the core protein. The 36-nucleotide insertion resulted in a new core protein with 12 extra amino acids at its amino-terminal end. A few scattered point mutations were clustered in the amino-terminal half of the core gene. Although the core protein of this hepatitis B virus variant carried immunologically detectable HBcAg, the absence of a humoral immune response to HBcAg could have been caused by previous infection with human immunodeficiency virus. This naturally occurring human hepatitis B virus variant replicated efficiently without expressing the precore region, confirming previous observations made of the artificial mutants of duck hepatitis B virus.
Bhat
R A
RA
Department of Laboratory Medicine, University of California, San Francisco 94143-0100.
Ulrich
P P
PP
Vyas
G N
GN
D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D004279:DNA, Viral / Q000235:genetics*; D006509:Hepatitis B / Q000382:microbiology*; D006510:Hepatitis B Antibodies / Q000032:analysis; D006512:Hepatitis B Core Antigens / Q000235:genetics / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics*; D006716:Homosexuality; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation
D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006512:Hepatitis B Core Antigens