B型肝炎病毒表面抗原在酵母菌分泌途徑表現所?生的生物效應

Abstract

B型肝炎病毒HBV(hepatitis B virus)在肝癌(hepatocellular carcinoma)發生上所扮演的角色以及對真核生物的影響仍不清楚。近年發現病毒的蛋白質會改變宿主基因的表現，進而導致肝癌的發生。過去本實驗室的研究發現，將一個帶有B型肝炎表面抗原(HBsAg)基因的質體送到酵母菌中，表現後使其進入酵母菌的分泌途徑(secretion pathway)中，會使得酵母菌的生長受到嚴重的抑制。本實驗篩選一株生長特別快速而且不受B型肺炎病毒表面抗原蛋白質毒性抑制的穩定轉形株NI(non-inhibited)。結果顯示NI具有較高的生長速率，飽和期(stationary phase)有較高的細胞存活率(cell viability)，缺糖飢餓(glucose starvation)時有較高的histone H1 kinase activity，較高的plasmid TRP1 marker Stability，較高的表面抗原(HBsAg)產量，偽絲狀生長(pseudohyphae growth)，及integration現象，使酵母菌變成類似癌細胞之生長模式。由於在肝癌的研究上一直缺乏良好的研究系統，無法進行深入的研究，酵母菌可以提供作為研究B型肝炎病毒(HBV)作用的研究系統。

The exact role of hepatitis B virus in the development of liver cancer is not clear. The recent identification of some viral regulatory genes suggest a possible direct involvement of the viral protein may alter host gene expression and lead to the development of hepatocellular carcinoma. According to previously study, yeast cells were transformed with a plasmid containing DNA fragment express the HBsAg gene in secretion pathway of yeast S. cerevisiae and it has been shown that the growth of these transformants are strongly inhibited. This study select a new population which are non-inhited (NI). These NI transformants were characterized in higher growth rate, higher cell viability, higher plasmid TRP1 marker stability, higher histone Hl kinase activity, pseudohyphae growth, HBV DNA integration. Because there is no good research system in liver cancer study, these results presented here suggest that these transformants is similar with cancer cells in cell growth and the S. cerevisiae may provide a simple system for studying the mechanism of action of HBV virus.