PMID- 16704298 OWN - NLM STAT- MEDLINE DCOM- 20060626 LR - 20231213 IS - 1079-9907 (Print) IS - 1079-9907 (Linking) VI - 26 IP - 4 DP - 2006 Apr TI - OAS and PKR are not required for the antiviral effect of Ad:IFN-gamma against acute HSV-1 in primary trigeminal ganglia cultures. PG - 220-5 AB - 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. FAU - Austin, Bobbie Ann AU - Austin BA AD - Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA. FAU - Halford, William AU - Halford W FAU - Silverman, Robert H AU - Silverman RH FAU - Williams, Bryan R G AU - Williams BR FAU - Carr, Daniel J J AU - Carr DJ LA - eng GR - R01 AI053108/AI/NIAID NIH HHS/United States GR - R01 AI034039/AI/NIAID NIH HHS/United States GR - P30 EY012190/EY/NEI NIH HHS/United States GR - EY12190/EY/NEI NIH HHS/United States GR - AI34039/AI/NIAID NIH HHS/United States GR - CA44059/CA/NCI NIH HHS/United States GR - R01 AI051414/AI/NIAID NIH HHS/United States GR - R01 CA044059/CA/NCI NIH HHS/United States GR - R01 AI051414-03/AI/NIAID NIH HHS/United States GR - AI053108/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - J Interferon Cytokine Res JT - Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research JID - 9507088 RN - 0 (Receptors, Interferon) RN - 82115-62-6 (Interferon-gamma) RN - EC 2.7.11.1 (eIF-2 Kinase) RN - EC 2.7.7.84 (2',5'-Oligoadenylate Synthetase) SB - IM MH - 2',5'-Oligoadenylate Synthetase/genetics/*physiology MH - Adenoviridae/genetics MH - Animals MH - Cells, Cultured MH - Genetic Vectors/genetics MH - *Herpesvirus 1, Human MH - Interferon-gamma/*genetics MH - Mice MH - Mice, Knockout MH - Mice, Transgenic MH - Receptors, Interferon/genetics MH - Trigeminal Ganglion/cytology/immunology/*virology MH - eIF-2 Kinase/genetics/*physiology MH - Interferon gamma Receptor PMC - PMC1472294 MID - NIHMS6004 EDAT- 2006/05/18 09:00 MHDA- 2006/06/27 09:00 PMCR- 2008/01/27 CRDT- 2006/05/18 09:00 PHST- 2006/05/18 09:00 [pubmed] PHST- 2006/06/27 09:00 [medline] PHST- 2006/05/18 09:00 [entrez] PHST- 2008/01/27 00:00 [pmc-release] AID - 10.1089/jir.2006.26.220 [doi] PST - ppublish SO - J Interferon Cytokine Res. 2006 Apr;26(4):220-5. doi: 10.1089/jir.2006.26.220.