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

The identified HFs were enriched for a range of cellular processes, such as transcription, gene expression, protein transport and cell cycle ( Figure S2 and S3) , and involved at different stages of viral infection. We investigated HFs involved in capsid transport and ubiquitination of antiviral intrinsic host defence factors in more detail. Incoming HSV-1 capsids are transported to nuclear pores via the microtubule-organizing centre (MTOC), mediated by capsid proteins VP26 (UL35) and UL46 binding to the dynein light chains DYNLT1 (Tctex1) and DYNLT3 (rp3) [54, 55] . Our Y2H screen confirmed the known interaction between the capsid protein VP26 and the dynein light chain DYNLT3 (Text S1 and Figure S4 ). Combined with the siRNA screen data, which found depletion of multiple light chain subunits had moderate anti-viral effects on HSV-1, these data confirm propositions of redundancy in the capsid transport process which ensures successful infection in the event of viral mutations [38, 39] , and provide further evidence that HSV-1 has evolved to be highly promiscuous in its exploitation of cellular pathways to its advantage.