Inactivation of the Scrapie Agent by Near Monochromatic Ultraviolet Light

Abstract

SCRAPIE is a progressive degenerative disease of the central nervous system of sheep. Because the disease is transmitted by cell-free filtrates the agent has been classified as a virus, but its response to many chemical and physical treatments has long been known to differ from that of “conventional” viruses. The transmitting agent increases greatly in quantity in the animal host. In the terminal stages of the disease in mice, preparations from the brain must usually be diluted by a factor of 10⁷–10⁸ to give an average of one mean lethal dose per unit volume, whatever the original inoculum to the affected mouse has been. Haig and Clarke¹, who used a substantial starting inoculum to follow the “growth” of the agent, showed an increase by a factor of 10⁴ in the titre of the agent in mouse brain by the time the terminal stage was reached. But experiments with ionizing and ultraviolet radiations led Alper et al.^2,3 to question whether the agent depended on replication of a nucleic acid moiety for proliferation, which was shown to occur also when the titre of the injected material had been reduced by irradiation in vitro⁴. The dose of ionizing radiation required to give an average of one inactivating event per infective unit was much larger, and the inferred “target volume” (molecular weight about 1.5 × 10⁵, ref. 2) therefore much smaller, than for any virus; if the “target” were nucleic acid, this molecular weight would be too low to allow of sufficient coding information for replication. With ultraviolet irradiation at 254 nm, detectable inactivation required doses which were very large compared with those which inactivated even the most “resistant” entities whose function depended on the integrity of nucleic acid^3,4. This suggested that the agent might be comparatively transparent to ultraviolet of wavelength in the “germicidal” region in which nucleic acids absorb most strongly.