US28-mediated activation of MAPKs and of PLCβ was also shown to mediate activation of the cAMP response element binding protein (CREB) in HEK-293 cells and COS-7 cells transiently transfected with US28 [31,38], a transcription factor linked to a broad range of cellular processes, such as cell proliferation, differentiation, survival, angiogenesis, immune response, migration and invasion [83] (Figure 2). Although this has not been proven in the context of HCMV infection, in HEK-293 cells transiently transfected with US28, this activation of CREB by US28 has also been reported to stimulate the major immediate early gene promoter/enhancer (MIE) [84], thus playing a key role in the activation and replication of HCMV, but also in HCMV reactivation from latency