Neuronal Interferon Signaling Is Required for Protection against Herpes Simplex Virus Replication and Pathogenesis

Interferon (ifn) responses are critical for controlling herpes simplex virus 1 (hsv-1). the importance of neuronal ifn signaling in controlling acute and latent hsv-1 infection remains unclear. compartmentalized neuron cultures revealed that mature sensory neurons respond to ifnβ at both the axon and cell body through distinct mechanisms,resulting in control of hsv-1. mice specifically lacking neural ifn signaling succumbed rapidly to hsv-1 corneal infection,demonstrating that ifn responses of the immune system and non-neuronal tissues are insufficient to confer survival following virus challenge. furthermore,neurovirulence was restored to an hsv strain lacking the ifn-modulating gene,γ34.5,despite its expected attenuation in peripheral tissues. these studies define a crucial role for neuronal ifn signaling for protection against hsv-1 pathogenesis and replication,and they provide a novel framework to enhance our understanding of the interface between host innate immunity and neurotropic pathogens. © 2015 rosato,leib.