title: Mechanism of the dependence of hepatitis B virus genotype G on co-infection with other genotypes for viral replication.
abstract: Hepatitis B virus (HBV) is classified into several genotypes. Genotype G (HBV/G) is characterised by worldwide dispersion, low intragenotypic diversity and a peculiar sequence of the precore and core region (stop codon and 36-nucleotide insertion). As a rule, HBV/G is detected in co-infection with another genotype, most frequently HBV/A2. In a previous in vivo study, viral replication of HBV/G was significantly enhanced by co-infection with HBV/A2. However, the mechanism by which co-infection with HBV/A2 enhances HBV/G replication is not fully understood. In this study, we employed 1.24-fold HBV/A2 clones that selectively expressed each viral protein and revealed that the core protein expressing construct significantly enhanced the replication of HBV/G in Huh7 cells. The introduction of the HBV/A2 core promoter or core protein or both genomic regions into the HBV/G genome showed that both the core promoter and core protein are required for efficient HBV/G replication. The effect of genotype on the interaction between foreign core protein and HBV/G showed that HBV/A2 was the strongest enhancer of HBV/G replication. Furthermore, Western blot analysis of Dane particles isolated from cultures of Huh7 cells co-transfected by HBV/G and a cytomegalovirus (CMV) promoter-driven HBV/A2 core protein expression construct indicated that HBV/G employed HBV/A2 core protein during particle assembly. In conclusion, HBV/G could take advantage of core proteins from other genotypes during co-infection to replicate efficiently and to effectively package HBV DNA into virions.
authors.affiliation: Department of Virology & Liver unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Sakamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Tanaka
authors.forename: T
authors.initials: T
authors.lastname: Watanabe
authors.forename: S
authors.initials: S
authors.lastname: Iijima
authors.forename: S
authors.initials: S
authors.lastname: Kani
authors.forename: M
authors.initials: M
authors.lastname: Sugiyama
authors.forename: S
authors.initials: S
authors.lastname: Murakami
authors.forename: K
authors.initials: K
authors.lastname: Matsuura
authors.forename: A
authors.initials: A
authors.lastname: Kusakabe
authors.forename: N
authors.initials: N
authors.lastname: Shinkai
authors.forename: F
authors.initials: F
authors.lastname: Sugauchi
authors.forename: M
authors.initials: M
authors.lastname: Mizokami
mesh_terms: D002460:Cell Line; D005838:Genotype; D006512:Hepatitis B Core Antigens / Q000235:genetics / Q000378:metabolism; D006515:Hepatitis B virus / Q000235:genetics* / Q000502:physiology*; D022781:Hepatocytes / Q000821:virology; D006801:Humans; D011401:Promoter Regions, Genetic; D019065:Virus Assembly; D014779:Virus Replication
chemical_list: D006512:Hepatitis B Core Antigens