The murine double-stranded RNA-dependent protein kinase PKR and the murine 2′,5′-oligoadenylate synthetase-dependent RNase L are required for IFN-β-mediated resistance against herpes simplex virus type 1 in primary trigeminal ganglion culture

Khaldun Al-Khatib, Bryan R.G. Williams, Robert H. Silverman, William Halford, Daniel J.J. Carr

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Abstract

A study was undertaken to evaluate the efficacy of an adenoviral construct expressing the murine interferon-β (IFN-β) transgene (Ad:IFN-β) 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-β 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-β 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-β 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.

Original languageEnglish
Pages (from-to)126-135
Number of pages10
JournalVirology
Volume313
Issue number1
DOIs
Publication statusPublished - 15 Aug 2003
Externally publishedYes

Keywords

  • Adenoviral vector
  • HSV-1
  • IFN-β
  • Neuron
  • OAS
  • PKR
  • Trigeminal ganglia

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