title: Replication advantage and host factor-independent phenotypes attributable to a common naturally occurring capsid mutation (I97L) in human hepatitis B virus.
abstract: Mutations of human hepatitis B virus (HBV) occur frequently within the capsid (core) protein in natural infections. The most frequent mutation of the core protein in HBV from Southeast Asia occurs at amino acid 97, changing an isoleucine (I) to a leucine (L). In our systematic study of virus-host interactions, we have examined the replication efficiency of a site-directed mutant, I97L, and its parental wild-type HBV in several different hepatoma cell lines. Interestingly, we found that this capsid variant replicated in human Huh7 hepatoma cells approximately 4.8-fold better than its parental wild-type HBV. A similar phenomenon was observed in another hepatoma cell line, J3. In addition, the level of encapsidated RNA pregenome in mutant I97L was about 5.7-fold higher than that of the wild-type HBV in Huh7 cells. Unlike Huh7 cells, no significant difference in viral DNA replication between the same I97L mutant and its parental wild-type HBV was observed in HepG2, a human hepatoblastoma cell line. This finding of a profound replication advantage for mutant I97L in Huh7 and J3 cells but not in HepG2 cells may have important implications for the emergence of this mutant in chronic HBV carriers. We speculate here that the mutation confers a host factor-independent growth advantage for the survival of HBV variants in gradually dedifferentiating hepatocytes and thus helps prolong viral persistence.
authors.affiliation: Center for Tropical Diseases and Sealy Center for Vaccine Development, Department of Pathology, University of Texas Medical Branch, Galveston, Texas 77555-0609, USA.
authors.forename: Fat-Moon
authors.initials: FM
authors.lastname: Suk
authors.forename: Min-Hui
authors.initials: MH
authors.lastname: Lin
authors.forename: Margaret
authors.initials: M
authors.lastname: Newman
authors.forename: Shann
authors.initials: S
authors.lastname: Pan
authors.forename: Sheng-Hsuan
authors.initials: SH
authors.lastname: Chen
authors.forename: Jean-Dean
authors.initials: JD
authors.lastname: Liu
authors.forename: Chiaho
authors.initials: C
authors.lastname: Shih
mesh_terms: D019943:Amino Acid Substitution; D036022:Capsid Proteins / Q000235:genetics*; D002353:Carrier State / Q000821:virology; D002460:Cell Line; D004279:DNA, Viral / Q000096:biosynthesis / Q000235:genetics; D019143:Evolution, Molecular; D006515:Hepatitis B virus / Q000145:classification / Q000235:genetics* / Q000254:growth & development / Q000502:physiology; D019694:Hepatitis B, Chronic / Q000821:virology; D006801:Humans; D009154:Mutation; D010641:Phenotype; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000235:genetics
chemical_list: D036022:Capsid Proteins; D004279:DNA, Viral; D012367:RNA, Viral