title: The murine double-stranded RNA-dependent protein kinase PKR and the murine 2',5'-oligoadenylate synthetase-dependent RNase L are required for IFN-beta-mediated resistance against herpes simplex virus type 1 in primary trigeminal ganglion culture.
abstract: A study was undertaken to evaluate the efficacy of an adenoviral construct expressing the murine interferon-beta (IFN-beta) transgene (Ad:IFN-beta) against herpes simplex virus type 1 (HSV-1) infection in a primary trigeminal ganglion (TG) cell culture. The transduction efficiency ranged from 0.2 to 11.0% depending on the multiplicity of infection (m.o.i.) of the adenoviral vector (0.5-50.0). Moreover, neurons were the main target of the adenoviral transduction. TG cultures transduced with Ad:IFN-beta displayed up to a 19-fold reduction in viral titers compared with cells transduced with an Ad:Null or nontransduced TG culture controls. Transduction with Ad:IFN-beta up-regulated two critical antiviral genes, double-stranded RNA-dependent protein kinase R (PKR) and 2',5'-oligoadenylate synthetase (OAS). The absence of PKR or RNase L (downstream effector molecule of OAS) attenuated Ad:IFN-beta efficacy against HSV-1 replication, implicating a critical role for PKR and OAS/RNase systems in the establishment of IFN-induced resistance against HSV-1 in TG cells.
authors.affiliation: Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
authors.forename: Khaldun
authors.initials: K
authors.lastname: Al-khatib
authors.forename: Bryan R G
authors.initials: BR
authors.lastname: Williams
authors.forename: Robert H
authors.initials: RH
authors.lastname: Silverman
authors.forename: William
authors.initials: W
authors.lastname: Halford
authors.forename: Daniel J J
authors.initials: DJ
authors.lastname: Carr
mesh_terms: D000256:Adenoviridae; D000818:Animals; D002478:Cells, Cultured; D004722:Endoribonucleases / Q000235:genetics / Q000502:physiology*; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors; D018259:Herpesvirus 1, Human / Q000187:drug effects / Q000502:physiology*; D016899:Interferon-beta / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D009474:Neurons / Q000821:virology; D014161:Transduction, Genetic; D012668:Trigeminal Ganglion / Q000821:virology*; D019892:eIF-2 Kinase / Q000235:genetics / Q000502:physiology*
chemical_list: D016899:Interferon-beta; D019892:eIF-2 Kinase; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease