title: Study of interferon-β antiviral activity against Herpes simplex virus type 1 in neuron-enriched trigeminal ganglia cultures.
abstract: Herpes simplex virus type 1 (HSV-1) causes a lytic infection in epithelial cells before being captured and moved via retrograde axonal transport to the nuclei of the sensory neurons of the trigeminal ganglion or dorsal root, where it establishes a latent infection. HSV-1 infection induces an antiviral response through the production of Beta Interferon (IFN-β) in infected trigeminal ganglia. The aim of this work was to characterize the response induced by IFN-β in neuron-enriched trigeminal ganglia primary cultures infected with HSV-1. An antiviral effect of IFN-β in these cultures was observed, including reduced viral production and increased cell survival. In contrast, viral infection significantly decreased both double stranded RNA dependent protein kinase (Pkr) transcription and Jak-1 and Stat-1 phosphorylation, suggesting a possible HSV-1 immune evasion mechanism in trigeminal cells. Additionally, HSV-1 infection upregulated Suppressor of Cytokine Signaling-3 (Socs3) mRNA; upregulation of socs3 was inhibited in IFN-β treated cultures. HSV-1 infection increased the number of Socs3 positive cells and modified the intracellular distribution of Socs3 protein, in infected cells. This neuron-enriched trigeminal ganglia culture model could be used to elucidate the HSV-1 viral cycle in sensory neurons and to study cellular antiviral responses and possible viral evasion mechanisms that underlie the choice between viral replication and latency.
authors.affiliation: Grupo de Virologia, Universidad El Bosque, Carrera 9 No. 131 A-02, Edificio de Biblioteca, Laboratorio 205, Bogotá D.C., Colombia. Electronic address: anamalowc@gmail.com.
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Low-Calle
authors.affiliation: Grupo de Virologia, Universidad El Bosque, Carrera 9 No. 131 A-02, Edificio de Biblioteca, Laboratorio 205, Bogotá D.C., Colombia. Electronic address: jpradaarismendy@yahoo.es.
authors.forename: Jeanette
authors.initials: J
authors.lastname: Prada-Arismendy
authors.affiliation: Grupo de Virologia, Universidad El Bosque, Carrera 9 No. 131 A-02, Edificio de Biblioteca, Laboratorio 205, Bogotá D.C., Colombia; Grupo de Patogénesis Infecciosa, Facultad de Odontología, Universidad Nacional de Colombia, Carrera 30 No. 45-03, Edificio 210 - Oficina 301, Bogotá D.C., Colombia. Electronic address: jecastellanosp@unal.edu.co.
authors.forename: Jaime E
authors.initials: JE
authors.lastname: Castellanos
mesh_terms: D000818:Animals; D002470:Cell Survival; D005260:Female; D020869:Gene Expression Profiling; D018259:Herpesvirus 1, Human / Q000276:immunology*; D057131:Immune Evasion; D016899:Interferon-beta / Q000276:immunology*; D051379:Mice; D008813:Mice, Inbred ICR; D009924:Organ Culture Techniques; D011984:Sensory Receptor Cells / Q000276:immunology / Q000821:virology; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000096:biosynthesis; D012668:Trigeminal Ganglion / Q000276:immunology* / Q000821:virology*; D014779:Virus Replication / Q000187:drug effects; D019892:eIF-2 Kinase / Q000096:biosynthesis
chemical_list: C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D016899:Interferon-beta; D019892:eIF-2 Kinase
keywords: 2′–5′ oligoadenylate synthetase; CM; HSV-1; HSV-1 glycoprotein B; Herpes simplex virus type 1; IFN; Interferon-β; Jak; Jak phosphorylated form; Jak-Stat; Janus kinase; Oas; Pkr; RNase-L; Signal Transduction and Activator of Transcription; Socs; Socs3; Stat; Stat phosphorylated form; TG; Trigeminal ganglion; complete medium; double stranded RNA-dependent protein kinase; gB; interferon; latent ribonuclease or 2′,5′-oligoisoadenylate synthetase-dependent RNAse; p-Jak; p-Stat; suppressor of cytokine signaling; trigeminal ganglion