- 作者: Chih-Ming Lin, Gen-Ming Wang, Guey-Mei Jow and Bing-Fang Chen
- 作者服務機構: 1School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan, R.O.C.
- 中文摘要: --
- 英文摘要:
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.
- 中文關鍵字: --
- 英文關鍵字: HBV; hepatocellular carcinoma; pre-S deletion; S promoter.