以過表現鈉離子牛磺膽酸共轉運蛋白之肝癌細胞株建立乙型與丁型肝炎病毒感染模型

Abstract

全球乙型肝炎病毒感染的患者目前估計約2.4億人，而慢性感染乙型肝炎病毒的病人有更高的風險發展為肝纖維化以及肝硬化並發展成肝癌等肝病；丁型肝炎病毒是乙型肝炎病毒的衛星病毒，在生活史中需要利用乙型肝炎病毒的外套膜進行感染，共同感染乙型與丁型肝炎則會加速進展成更嚴重的肝病，目前全世界約有1500到2000萬人感染丁型肝炎病毒，這兩種病毒在全球造成相當大的公共衛生議題。先前乙型或丁型肝炎的感染研究的困難之處在於沒有一個可以感染的小鼠模式也沒有一個適合感染的細胞株系統，在近期的研究發現到其中一個乙型肝炎的接受器-鈉離子牛磺膽酸共轉運蛋白 (NTCP)，並在實驗中證實可以提供乙型以及丁型肝炎病毒進入細胞。基於這項證據，本篇研究利用穩定過表現鈉離子牛磺膽酸共轉運蛋白的肝癌細胞株進行乙型以及丁型肝炎病毒的感染測試，檢查各個細胞株對於這兩種病毒的感染效率。研究中發現：在擁有相當的鈉離子牛磺膽酸共轉運蛋白表現量的情況下，從HepaG2 肝癌細胞株篩選出來SW1細胞和其他細胞株比較起來對於乙型肝炎病毒的感染有比較高的效率，而丁型肝炎病毒的感染似乎並不成功。利用目前的結果可以來推論表現鈉離子牛磺膽酸共轉運蛋白不一定能夠足以讓乙型或丁型肝炎進入細胞，不過利用目前建立的細胞株可以讓我們日後更進一步地分析其他促進這兩種肝癌病毒進入細胞的因子，或者是作為分析細胞對於病毒所產生抗病毒機制的工具。

There are approximately 240 million people are chronically infected with hepatitis B virus (HBV) worldwide. Patients who infected with HBV are at high risk for progression to cirrhosis and liver failure or liver cancer, and more than 780000 people die every year owing to the complications of HBV. Hepatitis Delta (HDV) virus is the smallest virus which can infect human. HDV is known to be a satellite virus of Hepatitis B virus (HBV), and it depends on envelope protein of HBV to process the entry and virus particle assembly in virus life cycle. HDV infection causes severe acute and chronic liver disease of HBV carriers. There are approximately 15 to 20 million people infected HDV (around 5% of HBs Ag carriers). Both HBV and HDV related liver diseases are still a major public health problem. There were no susceptible infection model of HBV and HDV because of lacking the knowledge of HBV entry. Recently, NTCP (sodium taurocholate cotransporting polypeptide) was identified as one of HBV entry receptors. Many studies showed that NTCP over expression rendered non-susceptible hepatoma cell lines susceptible to HBV and HDV. Thus our group generated the stably overexpressing ntcp HepaG2 cell line SW1 which is susceptible to HBV while with low efficiency to HDV. By taking advantage of this cell model, we can research other factors that involved in viral entry and the mechanism of antiviral pathways in the future.