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

Investigation into the effect of Med23 on interferon induction by qRT-PCR found that whilst Med23 over-expression induced IFNb (,3-fold increase), induction of IFN-l1 and l2/3 was considerably and statistically significantly higher (,26-fold induction; p = 0.003 and 0.002, respectively) ( Figure 4c ). This induction was specific, as levels of other cytokines and interferon-regulatory factors (IRFs) were unaffected by Med23 overexpression ( Figure S7a ). Secretion of IFN-l2/3 protein was also increased in all cell lines tested, but most significantly to ,11-fold in A549 cells (Figure 4d) , which is consistent with a recent report showing that type III interferons are the dominant type of IFNs expressed by primary airway epithelial cells [44] . Furthermore, qPCR analysis found depletion of Med23 inhibited the induction of IFN-l expression following HSV-1 infection of A549 cells in comparison to cells transfected with the RSCF siRNA control ( Figure 4e ). Together, these data suggest that IFN-l is responsible for the observed inhibitory effect of Med23 on HSV-1 replication.