Molecular Characterization of A New Variant of Hepatitis B Virus in A Persistently Infected Homosexual Man

Abstract

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.

Characteristics of Hepatitis B Virus Isolates of Genotype G and Their Phylogenetic Differences from the Other Six Genotypes (A through F)

“…Originally, HBV/G was identified in 11 of 82 (13%) HBV carriers in Georgia and 2 of 39 (5%) carriers from France (26). It does not appear to be a coincidence that the B1-89 isolate (11) is reported to be from France, the genotype of which is deduced to be G because of the 36-bp insertion in the C gene, and that an adw variant of probable genotype G, judged by the peculiar 36-bp insertion, was isolated from a homosexual carrier from San Francisco also infected with human immunodeficiency virus type 1 (1). Furthermore, all eight of the HBV/G isolates in the present study were recovered from patients living in San Francisco.…”

“…It may strike one as a big surprise that all eight of the HBV/G carriers examined in the present study possessed HBeAg in the serum as well. Moreover, HBeAg was detected in sera from two individuals from whom HBV/G isolates (B1-89 and an adw variant) were recovered (1,11).…”

Hepatitis B virus genotype G monoinfection and its transmission by blood components

“…Such sequences had already been described in a U.S. patient coinfected with HIV in 1990 and in an isolate (B1-89) from a French patient in 1991. 8,9 However, these isolates were not described as a new genotype. Genotype G was detected in 11 of 82 (13%) HBV carriers from Georgia (in the U.S.) and in 2 of 39 (5%) HBV-infected individuals in France.…”

Novel Type of Hepatitis B Virus Mutation: Replacement Mutation Involving a Hepatocyte Nuclear Factor 1 Binding Site Tandem Repeat in Chronic Hepatitis B Virus Genotype E

“…Furthermore, the insertions in the HBV genome can be of two types. The first one is the insertion of a nucleotide sequence which does not exist close to the affected sequence; examples include the 36-bp insertion observed in HBV genotype G (4,15,34) and the insertion of the hepatocyte nuclear factor 1 (HNF1) binding site (10,19,20,30). The second type is the insertion of a nucleotide sequence located close to the inserted portion, which is termed internal duplication or tandem repeat (10).…”