Abstract:
BACKGROUND:Naturally occurring pre-S deletion mutants have been identified in hepatitis B carriers and shown to be associated with the development of hepatocellular carcinoma. The phenotypes of these pre-S deletion genomes remain unclear, and they were investigated in this study. METHODS:The pre-S deletion genomes: (1) pre-S1 deletion, (2) deletion spanning pre-S1 and pre-S2, (3) pre-S2 N-terminal deletion, and (4) pre-S2 internal deletion were constructed and analyzed by transfection into Huh-7 cells. RESULTS:Functional analyses reveal that these mutants were divided into two groups: S promoter deletion and non-S promoter deletion variants. Compared with the wild-type genome, S promoter deletion variants led to an inverse ratio of pre-S1 mRNA and pre-S2/S mRNA, and intracellular accumulation of surface proteins. An interesting finding is that a small amount of L proteins was detected in the medium from S promoter deletion variant-transfected cells. Non-S promoter deletion variants conversely displayed a wild-type like mRNA and protein pattern. The secretion of surface proteins from non-S promoter deletion variants was inhibited less than from S promoter deletion variant. Immunofluorescence analysis showed mutant surface proteins colocalized with ER and exhibited an atypical distribution: granular staining pattern in the S-promoter deletion variants and perinuclear staining pattern in the non-S promoter deletion variants. CONCLUSION:This study shows that these pre-S deletion genomes exhibit two different phenotypes in mRNA transcription, surface protein expression and secretion. This diversity seems to result from the deletion of S promoter rather than result from the deletion of pre-S1 or pre-S2.
journal_name
J Biomed Scijournal_title
Journal of biomedical scienceauthors
Lin CM,Wang GM,Jow GM,Chen BFdoi
10.1186/1423-0127-19-17subject
Has Abstractpub_date
2012-02-07 00:00:00pages
17eissn
1021-7770issn
1423-0127pii
1423-0127-19-17journal_volume
19pub_type
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