title: Neuronal IFN signaling is dispensable for the establishment of HSV-1 latency.
abstract: IFN responses control acute HSV infection, but their role in regulating HSV latency is poorly understood. To address this we used mice lacking IFN signaling specifically in neural tissues. These mice supported a higher acute viral load in nervous tissue and delayed establishment of latency. While latent HSV-1 genome copies were equivalent, ganglia from neuronal IFN signaling-deficient mice unexpectedly supported reduced reactivation. IFNβ promoted survival of primary sensory neurons after infection with HSV-1, indicating a role for IFN signaling in sustaining neurons. We observed higher levels of latency associated transcripts (LATs) per HSV genome in mice lacking neuronal IFN signaling, consistent with a role for IFN in regulating LAT expression. These data show that neuronal IFN signaling modulates the expression of LAT and may conserve the pool of neurons available to harbor latent HSV-1 genome. The data also show that neuronal IFN signaling is dispensable for the establishment of latency.
authors: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
authors: Pamela C
authors: PC
authors: Rosato
authors: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
authors: Sarah
authors: S
authors: Katzenell
authors: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.
authors: Jean M
authors: JM
authors: Pesola
authors: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
authors: Brian
authors: B
authors: North
authors: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.
authors: Donald M
authors: DM
authors: Coen
authors: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA. Electronic address: david.a.leib@dartmouth.edu.
authors: David A
authors: DA
authors: Leib
mesh_terms: D000818:Animals; D002470:Cell Survival; D004195:Disease Models, Animal; D005724:Ganglia / Q000378:metabolism / Q000821:virology; D006561:Herpes Simplex / Q000378:metabolism* / Q000401:mortality / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000502:physiology*; D007372:Interferons / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism* / Q000821:virology*; D050794:STAT1 Transcription Factor / Q000172:deficiency; D015398:Signal Transduction; D019562:Viral Load; D017735:Virus Latency; D014779:Virus Replication
chemical_list: D050794:STAT1 Transcription Factor; D007372:Interferons
keywords: Herpes; Interferon; Latency; Neurons; Simplex