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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.
Insights
Researchers investigated the transmissible agent of Creutzfeldt-Jakob disease (CJD). The agent, not a conventional virus, showed resistance to various treatments but was sensitive to heat, confirming its unique nature.
Area of Science:
- Neuroscience
- Virology
- Prion Diseases
Background:
- Creutzfeldt-Jakob disease (CJD) is a fatal neurodegenerative disorder.
- The causative agent of CJD has historically been challenging to characterize, with early research exploring viral etiologies.
Purpose of the Study:
- To determine if conventional viruses are associated with Creutzfeldt-Jakob disease.
- To characterize the biological and physical properties of the CJD transmissible agent.
Main Methods:
- Inoculation of human and mouse-passaged CJD brain homogenates into nude mice.
- Inoculation of mouse-passaged CJD material into eight different tissue culture lines.
- Assessment of tissue cultures for cytopathic changes, hemadsorption, and reverse transcriptase activity.
- Evaluation of the CJD agent's resistance to chemical treatments (formalin, deoxycholate, Triton X-100, glutaraldehyde) and heat.
Main Results:
- No conventional viruses were detected in human or mouse-passaged CJD brain homogenates.
- Tissue cultures showed no signs of viral infection or replication.
- Nude mice inoculated with human CJD material developed disease identical to that in immunocompetent mice.
- The incubation period in mice was influenced by host genetics and inoculum size.
- The CJD agent demonstrated resistance to formalin, deoxycholate, and Triton X-100, but partial inactivation by glutaraldehyde and significant inactivation by heat (80°C and 100°C).
Conclusions:
- The transmissible agent of Creutzfeldt-Jakob disease is not a conventional virus.
- The agent's properties, including resistance to certain disinfectants and sensitivity to heat, provide crucial insights into its nature.
- Further characterization is needed to fully understand the non-viral agent responsible for CJD.