Lambda-Interferons Inhibit Herpes Simplex Virus Type 2 Replication in Human Cervical Epithelial Cells by Activating the JAK/STAT Pathway.

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-lambda s), 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-lambda s in human cervical epithelial cells remain unclear. In this study, we demonstrated potent inhibition of HSV-2 replication by IFN-lambda s without cytotoxicity. Investigation of the underlying mechanism(s) showed that IFN-lambda s induced expression of lFN-stimulated genes (ISGs) and enhanced the expression of several pattern recognition receptors (PRRs). Among the IFN-lambda s, IFN-lambda 3 induced higher levels of ISG and PRR expression. In addition, IFN-lambda s 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-lambda-mediated anti-HSV-2 activity and induction of ISGs and PRRs, whereas the induction of ISGs and PRRs by IFN-lambda s was not compromised by HSV-2 infection. These findings provide further experimental evidence that IFN-lambda s have therapeutic potential for HSV-2 infections.