Transcriptomic Analysis of Interferon Response in Toll-Like Receptor 2 Ligand-Treated and Herpes Simplex Virus 1-Infected Neurons and Astrocytes.

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-ß 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.

Innate immune response in astrocytes infected with herpes simplex virus 1.

Herpes simplex virus 1 (HSV-1), a double-stranded DNA virus, infects epithelial surfaces and establishes latency in the central nervous system, where astrocytes are a major immune cell type. Here, we report changes that occur in the expression of pathogen recognition receptors, such as Toll-like receptors, DNA and RNA sensors, interferons, and interferon-stimulated genes, when astrocytes are infected with HSV-1 strain F. We observed upregulation of Toll-like receptors 2, 6 and 9, MDA5, and DAI along with an increase in the expression of type I interferons and interferon-stimulated genes such as IFIT1, IFIT3 and RNase L. These genes encode proteins that mediate the antiviral immune response.