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

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. © 2012 lin et al; licensee biomed central ltd.