The Apoptotic Pathways Triggered by the 2A or 3C protease of Enterovirus 71

• Main Authors: Li-Te Hsu, 許立德
• Other Authors: Szu-Hao Kung
• Format: Others
• Language: zh-TW
• Published: 2005
• Online Access: http://ndltd.ncl.edu.tw/handle/66698733418306801084

碩士 === 國立陽明大學 === 醫學生物技術研究所 === 93 === Enterovirus 71 (EV71) is a causative agent for a number of childhood diseases, with the neurological syndromes such as encephalitis and meningitis being the most severe ones. Infection with EV71 or expression of its 2A or 3C protease (2Apro or 3Cpro) induces apoptotic cell death. To elucidate the mechanisms of the apoptosis elicited by either of the viral protease, plasmid that bears the viral protease coding region was transfected into HeLa cells. Expressions of either viral protease resulted in nuclear condensation and fragmentation, formation of DNA ladders and cleavage of poly(ADP-ribose) polymerase, hallmarks in the final stage of apoptosis. Caspase-3, an effector caspase was also activated by either of the viral protease. In cells expressing 2Apro, activation of the mitochondria-mediated apoptotic pathway was indicated by the activation of caspase-9 and Bid, increase in Bax as well as release of cytochrome C and apoptosis-inducing factor (AIF), while the levels of Bcl-2, Bad and deamination form of Bcl-xL remained unchanged. Similar patterns of apoptotic exhibitions were found in 3Cpro -expressing cells except that the level of bax was considered unaffected. A striking difference between cells expressing these two virus protease lay in p53 level where 2Apro appeared to elevate p53 expression at 24 h post-transfection (p.t.) and then p53 was slightly decreased to a normal level at 48 h p.t., while p53 level was found significantly declined at 48 h p.t in the 3Cpro–expressing cells. Induction of apoptosis by virus infection is emerging as an important aspect of pathogenesis. Moreover, discerning the triggers that initiate the apoptosis and the pathways involved should be of benefit to understanding of virus-cell interactions and virus pathology.