Functional analysis of hepatitis B virus pre-s deletion variants associated with hepatocellular carcinoma

التفاصيل البيبلوغرافية
العنوان: Functional analysis of hepatitis B virus pre-s deletion variants associated with hepatocellular carcinoma
المؤلفون: Lin, Chih-Ming, Wang, Gen-Ming, Jow, Guey-Mei, Chen, Bing-Fang
بيانات النشر: BioMed Central Ltd.
سنة النشر: 2012
المجموعة: BioMed Central
مصطلحات موضوعية: HBV, hepatocellular carcinoma, pre-S deletion, S promoter
الوصف: 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.
نوع الوثيقة: report
اللغة: English
العلاقة: http://www.jbiomedsci.com/content/19/1/17Test
الإتاحة: http://www.jbiomedsci.com/content/19/1/17Test
حقوق: Copyright 2012 Lin et al; licensee BioMed Central Ltd.
رقم الانضمام: edsbas.E3956D51
قاعدة البيانات: BASE