痘病毒進入細胞過程和膜融合之調控
I. 牛痘病毒膜融合複合物之研究
牛痘病毒是一種大型的包膜 DNA病毒,屬於痘病毒家族。牛痘病毒具有廣泛的宿主範圍,可在體內和體外感染不同類型的細胞。牛痘病毒粒子具有四個膜蛋白質,負責病毒附著於細胞表面,另外病毒有十一個蛋白質,共同組成一個病毒膜融合蛋白質複合物,以執行活化病毒膜融合的步驟。我們以前的工作集中在鑑定病毒附著蛋白質以及了解病毒被吞噬於細胞之後在細胞中運輸的過程。我們現在專注於研究牛痘病毒如何進行膜融合的機制。我們將會研究病毒膜融合複合物的各個成分蛋白在病毒進行膜融合過程中結構和功能之關係。此類研究亦將延伸於其他 DNA病毒,例如非洲豬瘟病毒。
II. 牛痘病毒膜融合抑制蛋白質之研究
病毒與細胞進行膜融合經常發生在細胞內的囊泡中,利用囊泡之酸化來誘導病毒融合蛋白質之結構產生改變,以執行膜融合的功用。我們最近的研究發現牛痘病毒在成熟病毒粒子上具有一個獨特的A26 蛋白質,在中性時抑制膜融合作用,唯有在酸化的過程中,A26上N端特定的His 胺基酸藉由質子化作用可以改變A26 的結構,使其不再抑制病毒融合蛋白質,從而活化膜融合。因此,牛痘苗病毒不僅具有復雜的膜融合蛋白複合物,而且具有獨特的融合抑制蛋白質,以調控病毒進入細胞過程中何時和何地開啟執行的膜融合活性。將來,探索其他病毒融合抑制蛋白的結構和功能之分析,也是我們未來的研究方向。
III. 寄主細胞訊息傳導在牛痘病毒感染,複製和散布過程中扮演的角色
當野生型牛痘病毒株感染小鼠骨髓衍生巨噬細胞(BMDM)時會誘導第1型干擾素產生。隨後的分析中發現刪除A26基因後(WRΔA26)感染BMDM 時卻能夠逃脫這種先天免疫之偵測。目前,我們試圖了解引起這種干擾素的訊息如何在此兩株病毒感染時產生差異。了解這些訊息傳導的作用,可以改善未來牛痘苗病毒作為疫苗載體或用於癌症治療之設計。
- PDF, 1989-1992, Center for Cancer Research, MIT, USA
- PDF, 1988, Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, USA
- Ph.D., 1988, Department of Microbiol. & Immunol., University of Washington at Seattle, USA
- BS, 1982, Department of Agriculture Chemistry, National. Taiwan University
- 2002, 中研院年輕學者研究成果獎
- 2006, 科技部傑出獎
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