title: OAS and PKR are not required for the antiviral effect of Ad:IFN-gamma against acute HSV-1 in primary trigeminal ganglia cultures.
abstract: Three interferon-gamma (IFN-gamma)-induced antiviral pathways have been reported. Involved antiviral proteins include: Mx, RNase L/2',5'-OAS, and protein kinase R (PKR). Involvement of OAS and PKR in IFN-gamma-induced anti-herpes simplex virus-1 (HSV-1) pathways has not been reported previously, but IFN-gamma induces OAS and PKR when other viruses invade the nervous system. The aim of the current study was to determine if the absence of intact OAS and PKR antiviral pathways affects the antiviral activity of IFN-gamma during acute HSV-1 infection within the trigeminal ganglia (TG). To investigate this, primary TG cultures were established using TGs removed from C57BL/6 (wild-type), RNase L knockout, and RNase L/PKR double knockout mice. Each dissociated TG was transduced with an adenoviral vector containing an IFN-gamma transgene or vector alone. Viral titers after HSV-1 infection of primary TG cell cultures were determined. Significant differences in viral titer for Ad:Null-transduced vs. Ad:IFN-gamma-tranduced TG were found in each genotype. However, the effectiveness of Ad:IFN-gamma was not reduced in the absence of both OAS and PKR pathways or OAS alone. Recombinant IFN-gamma also exhibited anti-HSV-1 activity. The effectiveness of the IFN-gamma transgene was lost in primary TG cells from IFN-gamma receptor knockout mice. The data suggest that novel anti-HSV-1 mechanisms are induced by IFN-gamma.
authors.affiliation: Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
authors.forename: Bobbie Ann
authors.initials: BA
authors.lastname: Austin
authors.forename: William
authors.initials: W
authors.lastname: Halford
authors.forename: Robert H
authors.initials: RH
authors.lastname: Silverman
authors.forename: Bryan R G
authors.initials: BR
authors.lastname: Williams
authors.forename: Daniel J J
authors.initials: DJ
authors.lastname: Carr
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics / Q000502:physiology*; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002478:Cells, Cultured; D005822:Genetic Vectors / Q000235:genetics; D018259:Herpesvirus 1, Human; D007371:Interferon-gamma / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D017471:Receptors, Interferon / Q000235:genetics; D012668:Trigeminal Ganglion / Q000166:cytology / Q000276:immunology / Q000821:virology*; D019892:eIF-2 Kinase / Q000235:genetics / Q000502:physiology*; D000096743:Interferon gamma Receptor
chemical_list: D015088:2',5'-Oligoadenylate Synthetase; D007371:Interferon-gamma; D017471:Receptors, Interferon; D019892:eIF-2 Kinase; D000096743:Interferon gamma Receptor