FIG. 7.

Binding of M-T5 to cellular Akt induces phosphorylation of Akt and is a key restriction determinant for MYXV permissiveness in type II human cancer cells. Phosphorylation of Akt at residue Thr308 by PDK1 induces a conformational change to Akt, which allows M-T5 to bind. Binding of M-T5 to the hemi-phosphorylated Akt promotes the subsequent phosphorylation of Ser473 by mTORC2. Once fully phosphorylated, Akt activates various downstream signaling cascades important for MYXV replication in the human cancer cells. Type I cells are constitutively in conformation IV and are permissive for both wild-type MYXV and vMyxT5KO. Type III cells are constitutively trapped in conformation I and are nonpermissive for both wild-type MYXV and vMyxT5KO.