Summary auto-generated
This study tracked prion distribution in Syrian hamsters following intraperitoneal inoculation with 263K scrapie prions. Researchers measured prion titers in lung and brain tissues at multiple timepoints over 133 days using bioassays. Lung prions were detected early in one animal at day 7 but remained undetectable until day 71, after which they appeared in all sampled animals at low levels. In contrast, brain prions were first detected at day 35 and increased exponentially with a doubling time of approximately 4-5 days, reaching an average titer of 10^8.0 LD50/g by day 127. Notably, two clinically normal hamsters on day 133 possessed prion titers in brain and lung indistinguishable from clinically affected animals. The authors suggest disruption of the blood-brain barrier during disease may allow prion entry into circulation and lung accumulation. These findings indicate that clinically normal animals in late incubation periods can harbor significant non-CNS prion titers, with important implications for identifying contamination risks in pharmaceuticals derived from infected animal tissues.
Key findings
- Lung prions remained undetectable or very low until day 71, while brain prions were detected by day 35 and increased exponentially with approximately 4-5 day doubling time
- Clinically normal hamsters at day 133 contained prion titers in brain and lung comparable to clinically affected animals, indicating significant prion accumulation precedes clinical symptoms
- Prion replication in brain following intraperitoneal infection proceeded more slowly (4-5 day doubling time) than following direct intracranial inoculation (2-8 day doubling time)
- The timing and pattern suggest blood-brain barrier disruption during disease course allows prion entry into systemic circulation and peripheral tissue accumulation
- Results highlight that negative bioassay results for extraneural tissues may reflect insufficient detection sensitivity rather than true absence of prions
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Abstract
Prion titres were measured in the lungs and brains of Syrian hamsters after intraperitoneal inoculation with sucrose gradient-purified 263K prions (approximately 10(8) LD50). Prions were detected in the lung of one hamster on day 7, but were not detected in the lungs of any other hamster until day 71. Prions were detected in the lungs of all hamsters sampled thereafter but titres remained low through day 127. Prions were first detected in the brain on day 35 and brain titres increased exponentially until day 127 with a doubling time of about 4.5 days. On day 133, titres averaged 10(8.0) LD50/g in brain and 10(5.0) LD50/g in lung. Two out of the five remaining hamsters were clinically normal but prion titres were not significantly different from those in the clinically affected hamsters. Thus, significant prion titres may be found outside the CNS in clinically normal hamsters.