A Systematic Analysis of Host Factors Reveals a Med23-Interferon-? Regulatory Axis against Herpes Simplex Virus Type 1 Replication

Griffiths, Samantha J.; Koegl, Manfred; Boutell, Chris; Zenner, Helen L.; Crump, Colin M.; Pica, Francesca; Gonzalez, Orland; Friedel, Caroline C.; Barry, Gerald; Martin, Kim; Craigon, Marie H.; Chen, Rui; Kaza, Lakshmi N.; Fossum, Even; Fazakerley, John K.; Efstathiou, Stacey; Volpi, Antonio; Zimmer, Ralf; Ghazal, Peter; Haas, Jürgen

One of the multi-protein complexes affecting HSV-1 replication was the Mediator complex, a large (.30 subunits) complex which links specific transcription factors to the RNA polymerase II transcription machinery [40] . As the requirement of Mediator subunits in the replication of herpes and other viruses is already well-known [7, 9, 11, 41] , it was striking that depletion of the Med23 subunit exerted the opposite phenotype and led to a strong increase in virus growth. The Mediator is composed of four distinct modules termed the head, middle, tail and kinase domains, which provide the Mediator with some degree of active control over transcription [59] . As individual subunits of this large complex interact with and exert functional effects via specific transcription factors, it is not unexpected that the observed antiviral effects were specific to Med23 [60] . Within the Mediator, Med23 forms a tight sub-complex with Med24 and Med16 [60, 61] . The increase in virus replication observed upon depletion of Med24 may be caused by the destabilisation of the structure of this sub-complex ( Figure S6b) .