Infection of human cancer cells with myxoma virus requires Akt activation via interaction with a viral ankyrin-repeat host range factor

被引:153
作者
Wang, G
Barrett, JW
Stanford, M
Werden, SJ
Johnston, JB
Gao, XJ
Sun, M
Cheng, JQ
McFadden, G
机构
[1] Univ Western Ontario, BioTherapeut Res Grp, Robarts Res Inst, London, ON N6G 2V4, Canada
[2] Univ Western Ontario, Dept Microbiol & Immunol, London, ON N6G 2V4, Canada
[3] Univ S Florida, Coll Med, Dept Pathol, Tampa, FL 33612 USA
[4] H Lee Moffit Canc Ctr & Res Inst, Tampa, FL 33612 USA
关键词
oncolytic virus; poxvirus; virus tropism; PkB; M-T5;
D O I
10.1073/pnas.0509341103
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
We demonstrate that the susceptibility of human cancer cells to be infected and killed by an oncolytic poxvirus, myxoma virus (MV), is related to the basal level of endogenous phosphorylated Akt. We further demonstrate that nonpermissive tumor cells will switch from resistant to susceptible for MV infection after expression of ectopically active Akt (Myr-Akt) and that permissive cancer cells can be rendered nonpermissive by blocking Akt activation with a dominant-negative inhibitor of Akt. Finally, the activation of Akt by MV involves the formation of a complex between the viral host range ankyrin-repeat protein, M-T5, and Akt. We conclude that the Akt pathway is a key restriction determinant for permissiveness of human cancer cells by MV.
引用
收藏
页码:4640 / 4645
页数:6
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