Small interfering RNA (siRNA) data associated with the following manuscript by Griffiths et al.(2013): A Systematic Analysis of Host Factors Reveals a Med23-Interferon-l Regulatory Axis against Herpes Simplex Virus Type 1 Replication. Herpes simplex virus type 1 (HSV-1) is a neurotropic virus causing vesicular oral or genital skin lesions, meningitis and other diseases particularly harmful in immunocompromised individuals. To comprehensively investigate the complex interaction between HSV-1 and its host we combined two genome-scale screens for host factors (HFs) involved in virus replication. A yeast two-hybrid screen for protein interactions and a RNA interference (RNAi) screen with a druggable genome small interfering RNA (siRNA) library confirmed existing and identified novel HFs which functionally influence HSV-1 infection. Hela cells were reverse-transfected with siRNA SMARTpools (4 siRNAs per gene). After 48 h the siRNAs were tested for cytotoxicity (3 replicates) or the capacity to influence replication of the HSV-1 GFP reporter virus C12 (6 replicates) from 24 to 80 h post-infection. Virus replication slopes during the linear phase were calculated and normalized to mock-transfected cells. Replication slopes were then compared to replication upon knockdown of essential (ICP4, VP16) or non-essential (VP11/12) viral genes, a cellular receptor for HSV-1 (HVEM) or control RISC-free siRNA (RSCF).Griffiths, Samantha; Koegl, Manfred; Boutell, Chris; Zenner, Helen; Crump, Colin; Pica, Francesca; Gonzalez, Orland; Friedel, Caroline; Barry, Gerald; Martin, Kim; Craigon, Marie; Chen, Rui; Kaza, Lakshmi; Fossum, Even; Fazakerley, John; Efstathiou, Stacey; Volpi, Antonio; Zimmer, Ralf; Ghazal, Peter; Haas, Jurgen. (2016). Small interfering RNAs (siRNA) genome-scale screen data for investigating host factors (HFs) involved in Herpes Simplex Virus Type 1 Replication, 2012-2013 [dataset]. University of Edinburgh. Medical school. Division of infection & Pathway Medicine. http://dx.doi.org/10.7488/ds/1451