Fig. 6

Speculative mechanism on how IFN-α inhibits VZV via interference of Mediator and IE62 within replication compartments. a During VZV infection, the major transactivator IE62 interacts with RNAP II, cellular transcription factor (TF) IID (TFIID), and the basal transcription complex which together form the replication compartment (RC) for viral DNA replication. Efficient VZV gene transcription requires recruitment of Mediator complex through IE62 and MED25 interaction which stabilizes RNAP II activity. Continuous translocation of MED25 into VZV RCs is essential for RC maturation (large globular pattern) and virion production. b IFN-α treatment impedes the formation of a stable complex between IE62 and Mediator complex, thus blocks RC maturation (small and large punctae). IFN-α induces the expression of CDK8 whose presence in RC may further inhibit the interaction between MED25 and IE62. Targeting the interaction between IE62 and MED25 (indicated by dashed arrow in a) may offer a novel approach to the development of antiviral agents against VZV infection