Journal
JOURNAL OF VIROLOGY
Volume 74, Issue 19, Pages 9099-9105Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.74.19.9099-9105.2000
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Funding
- NCI NIH HHS [R01 CA 70336, CA84217, R01 CA084217, R01 CA070336] Funding Source: Medline
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The functional significance of naturally occurring variants of human hepatitis B virus (HEV) remains largely unkown. 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,vith significantly reduced virion secretion get 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.
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