Delivery of Interferon-gamma by an adenovirus vector blocks herpes simplex virus Type 1 reactivation in vitro and in vivo independent of RNase L and double-stranded RNA-dependent protein kinase pathways.
HSV-1 is a significant human pathogen that can result in the loss of sight as a result of episodic reactivation of latent virus from sensory ganglion neurons. In this study the potential efficacy of anti-viral cytokine expression in preventing latent virus reactivation was investigated. Both type I (IFN-beta) and type II (IFN-gamma) IFN transgene expression following transduction of trigeminal ganglion explant cultures significantly reduced the incident of HSV-1 reactivation that in the case of IFN-beta was dependent on the presence of double stranded RNA-dependent protein kinase and RNase L. In vivo, expression of the IFN-gamma but not IFN-beta transgene significantly delayed and reduced the frequency of reactivation of latent mice exposed to UV light without discernable inflammation. This result is the first report that demonstrates the ability to block reactivation using an ectopic cytokine expression system and warrants further exploration as a means to prevent HSV-1 reactivation.
Carr
Daniel J J
DJ
Department of Ophthalmology, The University of Oklahoma Health Sciences Center, 608 Stanton L. Young Blvd., Oklahoma City, OK 73104, USA. dan-carr@ouhsc.edu
Austin
Bobbie A
BA
Halford
William P
WP
Stuart
Patrick M
PM
D000704:Analysis of Variance; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004722:Endoribonucleases / Q000172:deficiency / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage; D006561:Herpes Simplex / Q000235:genetics / Q000628:therapy*; D018259:Herpesvirus 1, Human / Q000502:physiology*; D016899:Interferon-beta / Q000235:genetics; D007371:Interferon-gamma / Q000008:administration & dosage* / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013997:Time Factors; D014161:Transduction, Genetic / Q000379:methods; D014466:Ultraviolet Rays; D014775:Virus Activation / Q000502:physiology* / Q000528:radiation effects; D019892:eIF-2 Kinase / Q000172:deficiency / Q000378:metabolism*
D016207:Cytokines; D016899:Interferon-beta; D007371:Interferon-gamma; D019892:eIF-2 Kinase; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease