title: Low-level secretion of human hepatitis B virus virions caused by two independent, naturally occurring mutations (P5T and L60V) in the capsid protein.
abstract: The functional significance of naturally occurring variants of human hepatitis B virus (HBV) remains largely unknown. Previously, we reported an immature secretion phenotype caused by a highly frequent mutation at amino acid 97 of the HBV core (capsid) protein (HBcAg). This phenotype is characterized by a nonselective and excessive secretion of virions containing an immature genome of single-stranded viral DNA. To extend our study of virion secretion to other naturally occurring variants, we have characterized mutations at HBcAg codons 5, 38, and 60 via site-directed mutagenesis. Although the phenotype of the mutation at codon 38 is nearly identical to that for the wild-type virus, our study reveals that a single mutation at codon 5 or 60 exhibits a new extracellular phenotype with significantly reduced virion secretion yet maintains normal intracellular viral DNA replication. A complementation study indicates that the mutant core protein alone is sufficient for the "low-secretion" phenotype. Furthermore, the low-secretion phenotype of the codon 5 mutant appears to be induced by the loss of a parental proline residue, rather than by the gain of a new amino acid. Our study underscores the core protein as another crucial determinant in virion secretion, in addition to the known envelope proteins. Our present results suggest that a very precise structure of both alpha-helical and nonhelical loop regions of the entire HBcAg molecule is important for virion secretion. The low-secretion variants may contribute to the phenomenon of gradually decreasing viremia in chronic carriers during the late phase of persistent infection.
authors.affiliation: Center for Tropical Diseases, Department of Pathology, University of Texas Medical Branch, Galveston, Texas 77555-0609, USA.
authors.forename: S
authors.initials: S
authors.lastname: Le Pogam
authors.forename: T T
authors.initials: TT
authors.lastname: Yuan
authors.forename: G K
authors.initials: GK
authors.lastname: Sahu
authors.forename: S
authors.initials: S
authors.lastname: Chatterjee
authors.forename: C
authors.initials: C
authors.lastname: Shih
mesh_terms: D002213:Capsid / Q000235:genetics*; D006515:Hepatitis B virus / Q000502:physiology*; D006801:Humans; D009154:Mutation; D014771:Virion / Q000502:physiology*; D014779:Virus Replication / Q000235:genetics