Sensing the storm: how inflammatory signalling drives reactivation of the human cytomegalovirus major immediate-early promoter

Seventy years after the discovery of human cytomegalovirus (HCMV), perhaps its most influential contribution to molecular biology remains the major immediate-early promoter (MIEP). A modified form of this powerful regulatory element is now used ubiquitously in biotechnology to drive protein expression, yet within the virus itself, the full promoter performs a far more complex task: governing the balance between latency and lytic replication. This review discusses our understanding of the transcription factors that regulate MIEP activation and repression and how this regulatory network shapes HCMV latency and reactivation.