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

G Wang, JW Barrett, M Stanford… - Proceedings of the …, 2006 - National Acad Sciences
G Wang, JW Barrett, M Stanford, SJ Werden, JB Johnston, X Gao, M Sun, JQ Cheng…
Proceedings of the National Academy of Sciences, 2006National Acad Sciences
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 …
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.
National Acad Sciences