title: Lambda-Interferons Inhibit Herpes Simplex Virus Type 2 Replication in Human Cervical Epithelial Cells by Activating the JAK/STAT Pathway.
abstract: Herpes simplex virus type 2 (HSV-2) is associated with a variety of diseases that are health problems worldwide. Our early study showed that lambda-interferons (IFN-λs), induced by the activation of the Toll-like receptor 3 and retinoic acid-inducible protein I signaling pathways, contribute to inhibition of HSV-2 replication in human cervical epithelial cells. However, anti-HSV-2 mechanisms and specific differences in signaling transduction by different IFN-λs in human cervical epithelial cells remain unclear. In this study, we demonstrated potent inhibition of HSV-2 replication by IFN-λs without cytotoxicity. Investigation of the underlying mechanism(s) showed that IFN-λs induced expression of IFN-stimulated genes (ISGs) and enhanced the expression of several pattern recognition receptors (PRRs). Among the IFN-λs, IFN-λ3 induced higher levels of ISG and PRR expression. In addition, IFN-λs up-regulated a number of genes that encode components of the Janus kinase signal transducers and activators of transcription (JAK/STAT) signaling pathway. Inhibition of the JAK/STAT signaling pathway by a JAK inhibitor abolished IFN-λ-mediated anti-HSV-2 activity and induction of ISGs and PRRs, whereas the induction of ISGs and PRRs by IFN-λs was not compromised by HSV-2 infection. These findings provide further experimental evidence that IFN-λs have therapeutic potential for HSV-2 infections.
authors.affiliation: Wuhan University School of Basic Medical Sciences.|Army 95377, PLA.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Li
authors.affiliation: Wuhan University School of Basic Medical Sciences.
authors.forename: Xuan
authors.initials: X
authors.lastname: Lu
authors.affiliation: Wuhan University School of Basic Medical Sciences.
authors.forename: Yufan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Wuhan University School of Basic Medical Sciences.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Cheng
authors.affiliation: Wuhan University School of Basic Medical Sciences.
authors.forename: Shi
authors.initials: S
authors.lastname: Liu
authors.affiliation: College of Biological Engineering, Hubei University of Technology.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: College of Biological Engineering, Hubei University of Technology.
authors.forename: Jingfeng
authors.initials: J
authors.lastname: Tang
authors.affiliation: Animal Biosafety Level III Laboratory at the Center for Animal Experiment, State Key Laboratory of Virology, Wuhan University.
authors.forename: Sijun
authors.initials: S
authors.lastname: Yang
authors.affiliation: Wuhan University School of Basic Medical Sciences.|Animal Biosafety Level III Laboratory at the Center for Animal Experiment, State Key Laboratory of Virology, Wuhan University.
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
mesh_terms: D000998:Antiviral Agents / Q000378:metabolism* / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004847:Epithelial Cells / Q000821:virology*; D005786:Gene Expression Regulation / Q000187:drug effects; D018258:Herpesvirus 2, Human / Q000276:immunology* / Q000502:physiology*; D006801:Humans; D007155:Immunologic Factors / Q000378:metabolism* / Q000633:toxicity; D007372:Interferons / Q000378:metabolism* / Q000633:toxicity; D015398:Signal Transduction / Q000187:drug effects; D014779:Virus Replication
chemical_list: D000998:Antiviral Agents; D007155:Immunologic Factors; D007372:Interferons
keywords: JAK/STAT signaling pathway; herpes simplex virus type 2; human cervical epithelial cells; interferon-stimulated genes; interferon-λ