title: A neuron-specific role for autophagy in antiviral defense against herpes simplex virus.
abstract: Type I interferons (IFNs) are considered to be the universal mechanism by which viral infections are controlled. However, many IFN-stimulated genes (ISGs) rely on antiviral pathways that are toxic to host cells, which may be detrimental in nonrenewable cell types, such as neurons. We show that dorsal root ganglionic (DRG) neurons produced little type I IFNs in response to infection with a neurotropic virus, herpes simplex type 1 (HSV-1). Further, type I IFN treatment failed to completely block HSV-1 replication or to induce IFN-primed cell death in neurons. We found that DRG neurons required autophagy to limit HSV-1 replication both in vivo and in vitro. In contrast, mucosal epithelial cells and other mitotic cells responded robustly to type I IFNs and did not require autophagy to control viral replication. These findings reveal a fundamental difference in the innate antiviral strategies employed by neurons and mitotic cells to control HSV-1 infection.
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Yordy
authors.forename: Norifumi
authors.initials: N
authors.lastname: Iijima
authors.forename: Anita
authors.initials: A
authors.lastname: Huttner
authors.forename: David
authors.initials: D
authors.lastname: Leib
authors.forename: Akiko
authors.initials: A
authors.lastname: Iwasaki
mesh_terms: D000818:Animals; D001343:Autophagy / Q000276:immunology*; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000276:immunology; D005727:Ganglia, Spinal / Q000166:cytology / Q000276:immunology / Q000821:virology; D006561:Herpes Simplex / Q000276:immunology / Q000821:virology; D018259:Herpesvirus 1, Human / Q000276:immunology* / Q000472:pathogenicity; D007370:Interferon Type I / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000276:immunology* / Q000821:virology*; D014779:Virus Replication
chemical_list: D007370:Interferon Type I