Dichotomy between survival and lytic gene expression in RNase L- and PKR-deficient mice transduced with an adenoviral vector expressing murine IFN-beta following ocular HSV-1 infection.
The present study investigated the role of interferon-inducible pathways in herpes simplex virus type 1-infected mice transduced with an adenoviral vector expressing murine interferon-beta (Ad:IFN-beta). Wild type mice or RNase L(-/-) mice deficient in responses to 2'-5' oligoadenylate synthetase activation, or lacking RNA-dependent protein kinase and transduced with Ad:IFN-beta showed enhanced survival following HSV-1 infection. The protective effect was associated with a reduction in viral gene expression in the cornea and trigeminal ganglion in wild type mice as well as the trigeminal ganglion of RNase L(-/-) mice. However, the efficacy of Ad:IFN-beta was lost in the corneas of RNase L(-/-) mice and significantly diminished in both the cornea and trigeminal ganglion as measured by viral gene expression in RNA-dependent protein kinase deficient mice. Collectively, the data suggest survival rates of viral-infected mice do not reflect the replication capacity as measured by herpes simplex virus type one lytic gene expression.
Al-Khatib
Khaldun
K
Department of Ophthalmology, Microbiology, and Immunology, University of Oklahoma Health Sciences Center, HSC608 Stanton L Young Blvd, Oklahoma City, OK 73104, USA.
Williams
Bryan R G
BR
Silverman
Robert H
RH
Halford
William
W
Carr
Daniel J J
DJ
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D004722:Endoribonucleases / Q000502:physiology; D005240:Feasibility Studies; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D018259:Herpesvirus 1, Human; D016899:Interferon-beta / Q000235:genetics* / Q000502:physiology; D016849:Keratitis, Herpetic / Q000201:enzymology / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D016019:Survival Analysis; D014161:Transduction, Genetic; D019892:eIF-2 Kinase / Q000502:physiology
D016899:Interferon-beta; D019892:eIF-2 Kinase; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease