Adenoviral proteins mimic nutrient/growth signals to activate the mTOR pathway for viral replication.

摘要: Like tumor cells, DNA viruses have had to evolve mechanisms that uncouple cellular replication from the many intra- and extracellular factors normally control it. Here we show adenovirus encodes two proteins activate mammalian target of rapamycin (mTOR) for viral replication, even under nutrient/growth factor-limiting conditions. E4-ORF1 mimics growth factor signaling by activating PI3-kinase, resulting in increased Rheb.GTP loading mTOR activation. E4-ORF4 is redundant with glucose stimulating mTOR, does not affect levels major mechanism whereby activates quiescent primary cells. We demonstrate activated through a dependent on protein phosphatase 2A-binding domain. also activation required efficient S-phase entry, independently E2F activation, adenovirus-infected These data reveal has evolved pathway, irrespective microenvironment, which play requisite role replication.