Abstract |
A study was undertaken to evaluate the efficacy of an adenoviral vector containing the murine interferon-beta (IFN-beta) transgene (Ad:IFN-beta) against herpes simplex virus type 1 (HSV-1) infection in two transduced cell lines. The transduction of the adenoviral vector efficiency, ranging from 2% to 100%, was dependent on the multiplicity of infection (moi) (0.4-50 plaque-forming units [pfu]/cell). Supernatants from cells transduced with the Ad:IFN-beta but not the adenoviral null vector (Ad:Null) contained biologically active IFN-beta (6.6-106 U/ml depending on the moi). Cells transduced with the Ad:IFN-beta displayed up to 25-fold reduction in viral titers compared with cells transduced with the Ad:Null or nontransduced cell controls. The suppression in viral titer correlated with a reduction in viral gene (alpha, beta, and gamma) and protein expression. The expression of IFN beta-responsive genes, including protein kinase R (PKR) and 2',5'-oligoadenylate synthetase (OAS), were significantly elevated in the Ad:IFN-beta-transduced cells by 12-fold and 25-fold, respectively. However, after infection with HSV-1, a transient but significant drop in PKR but not OAS gene expression was observed 10 h postinfection. The absence of PKR but not RNase L significantly attenuated the antiviral efficacy of the transgene. Collectively, these results illustrate the feasibility of employing a viral vector to deliver a potent antiviral gene to targeted cells without any obvious detriment to the vector itself and support an important role for PKR as a mediator of the anti-HSV-1 activity of type I IFN.
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Authors | Khaldun Al-Khatib, Bryan R G Williams, Robert H Silverman, William P Halford, Daniel J J Carr |
Journal | Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research
(J Interferon Cytokine Res)
Vol. 22
Issue 8
Pg. 861-71
(Aug 2002)
ISSN: 1079-9907 [Print] United States |
PMID | 12396725
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Recombinant Fusion Proteins
- Viral Proteins
- Interferon-beta
- eIF-2 Kinase
- 2',5'-Oligoadenylate Synthetase
- Endoribonucleases
- 2-5A-dependent ribonuclease
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Topics |
- 2',5'-Oligoadenylate Synthetase
(biosynthesis, genetics)
- Adenoviridae
(genetics)
- Animals
- Cell Line
(virology)
- Chlorocebus aethiops
- Endoribonucleases
(deficiency, physiology)
- Enzyme Induction
- Feasibility Studies
- Fibroblasts
(virology)
- Gene Expression Regulation, Viral
- Genetic Therapy
- Genetic Vectors
(genetics, pharmacology)
- Interferon-beta
(biosynthesis, genetics, physiology)
- L Cells
(virology)
- Mice
- Recombinant Fusion Proteins
(biosynthesis, physiology)
- Simplexvirus
(physiology)
- Transduction, Genetic
- Vero Cells
- Viral Proteins
(biosynthesis, genetics)
- eIF-2 Kinase
(biosynthesis, deficiency, genetics, physiology)
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