title: Cell type-dependent requirement of autophagy in HSV-1 antiviral defense.
abstract: Type I interferons (IFNs) are induced during most viral infections and are considered to be the primary and universal means of innate viral control. However, several other innate mechanisms, including autophagy, have recently been shown to play an important role in antiviral defense. In our recent study, we utilized a herpes simplex virus 1 (HSV-1) infection model to investigate the relationship between cell type and innate antiviral immune mechanisms. Our study demonstrates that dorsal root ganglion (DRG) neurons undergo an innate antiviral response to HSV-1 that differs from the antiviral program induced in mitotic cells in three distinct ways. First, DRG neurons produce less type I IFN and undergo a less effective IFN antiviral program vs. mitotic cells in response to HSV-1 infection. Second, the type I IFN program initiated in DRG neurons induces less cell death than in mitotic cells. Third, in the absence of a robust type I IFN response, DRG neurons, but not mitotic cells, rely on autophagy in HSV-1 defense. Our findings reveal a cell type-specific requirement for autophagy in defense against HSV-1, and offer insight into the cell-appropriate antiviral defense mechanism employed by neurons.
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Yordy
authors.forename: Akiko
authors.initials: A
authors.lastname: Iwasaki
mesh_terms: D000818:Animals; D001343:Autophagy; D005727:Ganglia, Spinal / Q000473:pathology; D018259:Herpesvirus 1, Human / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D051379:Mice; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000473:pathology; D009928:Organ Specificity; D014779:Virus Replication / Q000502:physiology
keywords: genital herpes; innate immunity; interferons; neurons; viral evasion