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

Virology. 2003 Aug 15;313(1):126-35. doi: 10.1016/s0042-6822(03)00298-8.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenoviridae
  • Animals
  • Cells, Cultured
  • Endoribonucleases / genetics
  • Endoribonucleases / physiology*
  • Female
  • Genetic Therapy
  • Genetic Vectors
  • Herpesvirus 1, Human / drug effects
  • Herpesvirus 1, Human / physiology*
  • Interferon-beta / biosynthesis*
  • Interferon-beta / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred ICR
  • Mice, Knockout
  • Neurons / virology
  • Transduction, Genetic
  • Trigeminal Ganglion / virology*
  • eIF-2 Kinase / genetics
  • eIF-2 Kinase / physiology*

Substances

  • Interferon-beta
  • eIF-2 Kinase
  • Endoribonucleases
  • 2-5A-dependent ribonuclease