title: Naturally occurring missense mutation in the polymerase gene terminating hepatitis B virus replication.
abstract: A hepatitis B virus (HBV) genome was cloned from human liver. Numerous mutations in all viral genes define this HBV DNA as a mutant, divergent from all known HBV DNA sequences. Functional analyses of this mutant demonstrated a defect blocking viral DNA synthesis. The genetic basis of this defect was identified as a single missense mutation in the 5' region of the viral polymerase gene, resulting in the inability to package pregenomic RNA into core particles. The replication defect could be trans-complemented by a full-length wild-type, but not by a full-length mutant or 3'-truncated wild-type, polymerase gene construct. Our findings indicate a critical role of the 5' polymerase gene region in the life cycle of the virus and suggest that introducing missense mutations in this region can be a strategy to terminate viral replication in vivo.
authors.affiliation: Molecular Hepatology Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown 02129.
authors.forename: H E
authors.initials: HE
authors.lastname: Blum
authors.forename: E
authors.initials: E
authors.lastname: Galun
authors.forename: T J
authors.initials: TJ
authors.lastname: Liang
authors.forename: F
authors.initials: F
authors.lastname: von Weizsäcker
authors.forename: J R
authors.initials: JR
authors.lastname: Wands
mesh_terms: D001483:Base Sequence; D004279:DNA, Viral / Q000378:metabolism; D004259:DNA-Directed DNA Polymerase / Q000096:biosynthesis / Q000235:genetics*; D015870:Gene Expression; D005814:Genes, Viral; D005816:Genetic Complementation Test; D006515:Hepatitis B virus / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D012367:RNA, Viral / Q000096:biosynthesis; D014779:Virus Replication / Q000235:genetics*
chemical_list: D004279:DNA, Viral; D012367:RNA, Viral; D004259:DNA-Directed DNA Polymerase