行政院國家科學委員會補助專題研究計畫成果報告:B型肝炎表面抗原突變株的細胞生物學及免疫學意義（３／３）

We have previously identified several pre-S mutants in ground glass hepatocytes (GGH) at different replicative stages of chronic HBV infection. The differential expression patterns of hepatocytes expressing surface antigen encourage us to pursue its underlying biologic significance. Two major types of pre-S mutants were identified. Type Ι GGH contains pre-S1 deletion mutant and usually sporadically distributes while Type ΙΙ GGH contains pre-S2 deletion mutant, consistently clusters in groups, and emerges at the late non-replicative phase. The surface antigen in both types of GGH localizes in ER. In vitro transfection and expression of pre-S1 and pre-S2 mutants revealed an expression pattern mimicking that in liver tissues. The expression of pre-S mutants in ER led to an enhanced expression of ER stress signals GRP78/94, PERK, and JNK. By flow cytometry analysis, the induction of ER stress will lead to cell cycle arrest for pre-S1 mutant but not for pre-S2 mutant, suggesting that pre-S2 mutant showed an enhanced growth potential. Agarose colony assay of pre-S mutants on a primary hepatocyte cell line HH4 demonstrated an enhanced colony formation for pre-S mutants, particularly for the pre-S2 mutant. Therefore, the different types of GGH do contain specific pre-S mutants which may exhibit differential cell cycle regulation and transforming capability