Herpes simplex virus (HSV)-1 infection causes cold sores and keratitis. Upon infection, it forms lesions at the epithelium and enters neurons where it establishes a latent infection. Host innate immune receptor Toll-like receptor (TLR)2 recognizes HSV by sensing its glycoproteins and induces an innate immune response. Upon activation, TLR2 forms a dimer with TLR1, TLR2, or TLR6 and signals inducing cytokines and interferons (IFNs). In this study, we checked the effect of differential activation of TLR2 by using different TLR2 dimer-specific ligands on the anti-HSV-1 innate immune response. We found that TLR2/2 ligand-induced IFN-β in neurons, while IFN-α in astrocytes and these IFNs subsequently induce the expression of IFN stimulatory genes like viperin, Ch25H, OAS2, latent RNase (RNase L), protein kinase R (PKR), and interferon-induced proteins with tetratricopeptide repeats (IFIT) 1. These are the genes with antiviral functions such as blocking viral attachment, protein synthesis, and egress.
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