抄録
Herpes Simplex Virus Type 2 (HSV-2) is associated with a variety of diseases, resulting in world-wide health problems. Our early study showed that lambda-interferons (IFN-λs) induced by activation of the toll-like receptors 3/ retinoic acid-inducible protein I (TLR3/RIG-I) signaling pathways contribute to inhibition of HSV-2 replication in the human cervical epithelial cells. However, anti-HSV-2 mechanisms and specific differences in signaling transduction by different IFN-λs in human cervical epithelial cells are unclear. In this study, we demonstrated that IFN-λs could potently inhibit HSV-2 replication without cytotoxicity. Investigation of the mechanism(s) showed that IFN-λs induced expression of IFN stimulated genes (ISGs) and also enhanced the expression of several pattern recognition receptors (PRRs). Among these IFN-λs members, IFN-λ3 induced higher levels of ISGs and PRRs expression. In addition, IFN-λs upregulated a number of genes for components of the Janus kinase signal transducers and activators of transcription (JAK/STAT) signaling pathway. Inhibition of JAK/STAT signaling pathway by a JAK inhibitor abolished IFN-λs mediated anti-HSV-2 activity and induction of the ISGs and PRRs. Whereas the induction by IFN-λs of ISGs and PRRs was not compromised by HSV-2 infection. These findings provide further experimental evidence that IFN-λs have therapeutic potential for treatment of HSV-2 infection.
