title: Neuronal Interferon Signaling Is Required for Protection against Herpes Simplex Virus Replication and Pathogenesis.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, United States of America.
authors.forename: Pamela C
authors.initials: PC
authors.lastname: Rosato
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, United States of America.
authors.forename: David A
authors.initials: DA
authors.lastname: Leib
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005455:Fluorescent Antibody Technique; D006561:Herpes Simplex / Q000276:immunology*; D018259:Herpesvirus 1, Human / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology; D016899:Interferon-beta / Q000276:immunology*; D051379:Mice; D009474:Neurons / Q000276:immunology* / Q000821:virology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*; D014779:Virus Replication / Q000276:immunology
chemical_list: D016899:Interferon-beta