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Virological characteristics of hepatitis B genotype G/A2 recombination virus in Japan
Author(s) -
Tsuzuki Yuji,
Watanabe Tsunamasa,
Iio Etsuko,
Fujisaki Seiichiro,
Ibe Shiro,
Kani Satomi,
HamadaTsutsumi Susumu,
Yokomaku Yoshiyuki,
Iwatani Yasumasa,
Sugiura Wataru,
Okuse Chiaki,
Okumura Akihiko,
Sato Yoshihisa,
Tanaka Yasuhito
Publication year - 2016
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/hepr.12612
Subject(s) - virology , genotype , biology , hepatitis b virus , genotyping , recombinant dna , homologous recombination , orthohepadnavirus , superinfection , virus , hepadnaviridae , genetics , gene
Abstract Aim We identified four cases of infection with hepatitis B virus genotype G and A2 recombinant (HBV/G/A2) strains, which were initially overlooked by enzyme immunoassay‐based genotyping. The patients were all men who have sex with men (MSM) and inhabited several metropolitan areas of Japan, suggesting that the recombinant strains may be circulating among high‐risk groups such as MSM. Here, we investigated the genomic structure and virological properties of the HBV/G/A2 strains. Methods Complete genome sequences of the isolates were determined and phylogenetically analyzed. Replication efficiency of HBV/G/A2 was investigated by transfecting plasmids containing 1.24‐fold viral genome. The in vivo viral kinetics of HBV/G/A2 were investigated using chimeric mice with humanized livers. Results Phylogenetic analysis revealed that the four strains were almost identical (>99.7% homologous). The preS2/S region of these strains was highly homologous to that of genotype A2 and the remaining region was almost identical to that of genotype G, reflecting inter‐genotypic recombination. Interestingly, in all four cases, genotype A was co‐infected as a minor population. In vitro analysis revealed that HBV/G/A2 had a low replication rate. Although detectable viremia was not measurable following the inoculation of HBV/G/A2 into chimeric mice, subsequent superinfection of HBV genotype A greatly enhanced HBV/G/A2 replication and viral spread. Conclusion We found that four cases of HBV/G/A2 recombinant among MSM patients in the metropolitan areas of Japan, and HBV/A co‐infections are required for its efficient replication. High‐risk groups such as MSM should be carefully tested for infection of genotype G‐derived variants.