[HTML][HTML] Neuronal interferon signaling is required for protection against herpes simplex virus replication and pathogenesis

PC Rosato, DA Leib - PLoS pathogens, 2015 - journals.plos.org
PLoS pathogens, 2015journals.plos.org
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 …
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.
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