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Pathogenesis of scrapie: agent multiplication in brain at the first and second passage of hamster scrapie in mice
Abstract:
The intracerebral (i.c.) injection of mice with a particular source of hamster passaged scrapie produced disease after an incubation period of 325 +/- 6 days (mean +/- s.e.). The incubation period at the second i.e. passage in mice was reduced to 149 +/- 2 days. Studies were made of the dynamics of agent replication at 1st and 2nd passages in mice. At first passage, there was a 'zero phase' lasting about 175 days, when no infectious agent was detected in brain (or spleen), followed by a period of agent replication which lasted 150 days. At second passage, there was no significant 'zero phase' and agent replication occupied the whole of the incubation period. The occurrence of a 'zero phase' on interspecies passage of scrapie is discussed in relation to other reports of a 'zero phase' in mouse passaged scrapie.
Insights
Hamster-passaged scrapie in mice showed a prolonged incubation period initially, with a
Area of Science:
- Neuroscience
- Virology
- Infectious Diseases
Background:
- Scrapie is a transmissible spongiform encephalopathy (TSE) affecting animals.
- Interspecies transmission of TSE agents can alter disease characteristics.
- Understanding agent replication dynamics is crucial for TSE research.
Purpose of the Study:
- To investigate the replication dynamics of hamster-passaged scrapie agent in mice.
- To characterize the incubation period and 'zero phase' during primary and secondary passages in mice.
Main Methods:
- Intracerebral inoculation of mice with hamster-passaged scrapie.
- Monitoring of disease onset and incubation periods.
- Assessment of infectious agent presence in brain and spleen over time.
Main Results:
- First passage in mice resulted in a long incubation period (325 days) with a 'zero phase' of 175 days before agent replication.
- Second passage significantly reduced the incubation period to 149 days, with no significant 'zero phase'.
- Agent replication occupied the entire incubation period during the second passage.
Conclusions:
- Interspecies passage of scrapie agent into a new host (mice) can lead to a 'zero phase' where the agent is not detectable.
- Subsequent passages in the new host reduce or eliminate this 'zero phase', altering agent replication dynamics.
- The findings contribute to understanding the adaptation and replication of TSE agents during host adaptation.