Evidence for an unconventional virus in mouse-adapted Creutzfeldt-Jakob disease

Abstract

Homogenates of a human brain from a case of Creutzfeldt-Jakob disease and a homogenate of mouse brains from mouse passage 1 of the disease in mice contained no detectable conventional viruses. Both human material and mouse-passaged material were inoculated into nude mice, and the mouse-passaged material was also inoculated into eight different tissue culture lines. The tissue cultures showed no cytopathic changes or hemadsorption and failed to produce an increased amount of reverse transcriptase. The nude mice inoculated with human brain suspensions developed a disease identical to that in immunocompetent mice, with a nearly identical incubation period of 9 to 13 months. The incubation period of the disease in mice was under host genetic control and was, additionally, directly related to the inoculum size. The agent was resistant to 10% Formalin, 5% deoxycholate, 1% Triton X-100, and 5% glutaraldehyde; however, glutaraldehyde treatment resulted in a significant loss of infectivity. Approximately 1 log of infectivity was lost by heating brain suspensions to 80 degrees C for 15 min, with no additional loss upon further incubation up to 45 min. Heating at 100 degrees C for 15 min led to a 3-log loss of infectivity.