Hepatitis C virus NS3-4A protein regulates apoptosis of host cells
碩士 === 國立臺灣大學 === 微生物學研究所 === 96 === Hepatitis C virus (HCV) NS3 is a nonstructural protein that possesses protease and RNA helicase activity. NS4A is a cofactor of NS3 protease, it promotes HCV polyprotein processing and NS3 internal cleavage. NS3-4A can localize at mitochondria to cleave the mitoc...
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ndltd-TW-096NTU053810572016-05-11T04:16:52Z http://ndltd.ncl.edu.tw/handle/02305177921626840422 Hepatitis C virus NS3-4A protein regulates apoptosis of host cells C型肝炎病毒非結構性蛋白質NS3-4A對於宿主細胞之細胞凋亡的調節作用 Yu-Ching Lin 林育靜 碩士 國立臺灣大學 微生物學研究所 96 Hepatitis C virus (HCV) NS3 is a nonstructural protein that possesses protease and RNA helicase activity. NS4A is a cofactor of NS3 protease, it promotes HCV polyprotein processing and NS3 internal cleavage. NS3-4A can localize at mitochondria to cleave the mitochondria protein MAVS/IPS-1 then to block the type-I IFN-b pathway. NS4A was also found to accumulate on mitochondria membrane and induce mitochondria-mediated apoptosis. In this study, HepG22-NS3-4A inducible cell line was established. Expression of NS3-4A protein in the stable line resulted in a cleavage of NS3-4A protein and partial colocalization of the NS3 and NS4A to the mitochondria. Expression of NS3-4A also restored the mitochondria membrane potential collapsed by DCA both in the inducible HepG22-NS3-4A cell line and in 293 transient transfection system. Both cytochrome c release and caspase-3 activity induced by DCA can be repressed by NS3-4A, but NS3-4A can not protect the DCA-induced DNA fragmentation. Further dissection indicated that NS3 or NS4A alone can restore the mitochondria membrane potential collapse by DCA. NS4A can decrease the DCA-induced cytochrome c release. The mechanisms involved in the NS3-4A mediated anti-apoptotic effects are not completely understood. Nevertheless, it was reported that mitochondria p53 can promote mitochondria-mediated apoptosis. The observation that the level of p53 at mitochondrial fraction was lower in the NS3-4A expressing cells than that of the control cells, suggesting that p53 maybe a target of the NS3-4A regulated anti-apoptotic effect. 張鑫 2008 學位論文 ; thesis 51 zh-TW |
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碩士 === 國立臺灣大學 === 微生物學研究所 === 96 === Hepatitis C virus (HCV) NS3 is a nonstructural protein that possesses protease and RNA helicase activity. NS4A is a cofactor of NS3 protease, it promotes HCV polyprotein processing and NS3 internal cleavage. NS3-4A can localize at mitochondria to cleave the mitochondria protein MAVS/IPS-1 then to block the type-I IFN-b pathway. NS4A was also found to accumulate on mitochondria membrane and induce mitochondria-mediated apoptosis. In this study, HepG22-NS3-4A inducible cell line was established. Expression of NS3-4A protein in the stable line resulted in a cleavage of NS3-4A protein and partial colocalization of the NS3 and NS4A to the mitochondria. Expression of NS3-4A also restored the mitochondria membrane potential collapsed by DCA both in the inducible HepG22-NS3-4A cell line and in 293 transient transfection system. Both cytochrome c release and caspase-3 activity induced by DCA can be repressed by NS3-4A, but NS3-4A can not protect the DCA-induced DNA fragmentation. Further dissection indicated that NS3 or NS4A alone can restore the mitochondria membrane potential collapse by DCA. NS4A can decrease the DCA-induced cytochrome c release. The mechanisms involved in the NS3-4A mediated anti-apoptotic effects are not completely understood. Nevertheless, it was reported that mitochondria p53 can promote mitochondria-mediated apoptosis. The observation that the level of p53 at mitochondrial fraction was lower in the NS3-4A expressing cells than that of the control cells, suggesting that p53 maybe a target of the NS3-4A regulated anti-apoptotic effect.
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張鑫 |
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張鑫 Yu-Ching Lin 林育靜 |
author |
Yu-Ching Lin 林育靜 |
spellingShingle |
Yu-Ching Lin 林育靜 Hepatitis C virus NS3-4A protein regulates apoptosis of host cells |
author_sort |
Yu-Ching Lin |
title |
Hepatitis C virus NS3-4A protein regulates apoptosis of host cells |
title_short |
Hepatitis C virus NS3-4A protein regulates apoptosis of host cells |
title_full |
Hepatitis C virus NS3-4A protein regulates apoptosis of host cells |
title_fullStr |
Hepatitis C virus NS3-4A protein regulates apoptosis of host cells |
title_full_unstemmed |
Hepatitis C virus NS3-4A protein regulates apoptosis of host cells |
title_sort |
hepatitis c virus ns3-4a protein regulates apoptosis of host cells |
publishDate |
2008 |
url |
http://ndltd.ncl.edu.tw/handle/02305177921626840422 |
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