| Virus Name | Human herpesvirus 1 |
| Virus Short Name | HSV1 |
| Order | Herpesvirales |
| Virus Family | Herpesviridae |
| Virus Subfamily | Alphaherpesvirinae |
| Genus | Simplexvirus |
| Species | Herpes simplex virus 1 |
| Host | Human, mammals |
| Cell Tropism | Primary site of infection: epithelial mucosal cells , latency: remains latent in sensory neurons (ganglions) |
| Associated Disease | Skin vesicles or mucosal ulcers, rarely encephalitis and meningitis |
| Mode of Transmission | Contact, saliva |
| VIPR DB link | http://www.viprbrc.org/brc/vipr_allSpecies_search.do?method=SubmitForm&decorator=herpes |
| ICTV DB link | https://talk.ictvonline.org/ictv-reports/ictv_9th_report/dsdna-viruses-2011/w/dsdna_viruses/91/herpesviridae |
| Virus Host DB link | http://www.genome.jp/virushostdb/view/?virus_lineage=Herpesviridae |
| Paper Title | A systematic analysis of host factors reveals a Med23-Interferon-lambda regulatory axis against herpes simplex virus Type 1 replication |
| Author's Name | Samantha J. Griffiths, Manfred Koegl, Chris Boutell, Helen L. Zenner, Colin M. Crump, Francesca Pica, Orland Gonzalez, Caroline C. Friedel, Gerald Barry, Kim Martin, Marie H. Craigon, Rui Chen, Lakshmi N. Kaza, Even Fossum, John K. Fazakerley, Stacey Efstathiou, Antonio Volpi, Ralf Zimmer, Peter Ghazal, Ju rgen Haas |
| Journal Name | PLOS Pathogens |
| Pubmed ID | 23950709 |
| Abstract | 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. Bioinformatic analyses found the 358 HFs were enriched for several pathways and multi-protein complexes. Of particular interest was the identification of Med23 as a strongly anti-viral component of the largely pro-viral Mediator complex, which links specific transcription factors to RNA polymerase II. The anti-viral effect of Med23 on HSV-1 replication was confirmed in gain-of-function gene overexpression experiments, and this inhibitory effect was specific to HSV-1, as a range of other viruses including Vaccinia virus and Semliki Forest virus were unaffected by Med23 depletion. We found Med23 significantly upregulated expression of the type III interferon family (IFN-lambda) at the mRNA and protein level by directly interacting with the transcription factor IRF7. The synergistic effect of Med23 and IRF7 on IFN-lambda induction suggests this is the major transcription factor for IFN-lambda expression. Genotypic analysis of patients suffering recurrent orofacial HSV-1 outbreaks, previously shown to be deficient in IFN-lambda secretion, found a significant correlation with a single nucleotide polymorphism in the IFN-lambda3 (IL28b) promoter strongly linked to Hepatitis C disease and treatment outcome. This paper describes a link between Med23 and IFN-lambda, provides evidence for the crucial role of IFN-lambda in HSV-1 immune control, and highlights the power of integrative genome-scale approaches to identify HFs critical for disease progression and outcome. |
| Used Model | HeLa cell |
| DOI | 10.1371/journal.ppat.1003514 |
