High incidence of scrapie induced by repeated injections of subinfectious prion doses
Related Experiment Video
Updated: Aug 17, 2026
Procedures for Identifying Infectious Prions After Passage Through the Digestive System of an Avian Species
Published on: November 6, 2013
Catherine Jacquemot1, Céline Cuche, Dominique Dormont
1Neurovirologie et Régénération du Système Nerveux, Dpt Neurosciences, Institut Pasteur, Paris, France.
Abstract:
To clarify the mechanisms leading to the development of Creutzfeldt-Jakob disease in some recipients of pituitary-derived human growth hormone (hGH), we investigated the effects of repeated injections of low prion doses in mice. The injections were performed, as in hGH-treated children, by a peripheral route at short intervals and for an extended period. Twelve groups of 24 mice were intraperitoneally inoculated one, two, or five times per week for 200 days with 2 x 10(-5) to 2 x 10(-8) dilutions of brain homogenate containing the mouse-adapted C506M3 scrapie strain. Sixteen control mice were injected once a week for 200 days with a 2 x 10(-4) dilution of normal brain homogenate. Of mice injected in a single challenge with a scrapie inoculum of a 2 x 10(-4), 2 x 10(-5), or 2 x 10(-6) dilution, 2/10, 1/10, and 0/10 animals developed scrapie, respectively. Control mice remained healthy. One hundred thirty-five of 135 mice injected with repeated prion doses of a 2 x 10(-5) or 2 x 10(-6) dilution succumbed to scrapie. Of mice injected with repeated scrapie doses of a 2 x 10(-7) or 2 x 10(-8) dilution, 52/59 and 38/67 animals died of scrapie, respectively. A high incidence of scrapie was observed in mice receiving repeated doses at low infectivity, whereas there was no disease in mice that were injected once with the same doses. Repeated injections of low prion doses thus constitute a risk for development of prion disease even if the same total dose inoculated in a single challenge does not induce the disease.
Insights
Repeated low-dose prion injections increase prion disease risk in mice, even when a single dose is insufficient. This highlights the danger of cumulative exposure, mimicking human growth hormone treatments.
Area of Science:
- Neuroscience
- Infectious Diseases
- Biochemistry
Background:
- Creutzfeldt-Jakob disease (CJD) transmission linked to pituitary-derived human growth hormone (hGH).
- Mechanisms of prion disease development require further clarification.
Purpose of the Study:
- Investigate the effect of repeated low-dose prion injections on disease development.
- Mimic peripheral administration routes and short intervals used in hGH therapy.
Main Methods:
- Mice received repeated intraperitoneal injections of varying dilutions of mouse-adapted scrapie strain.
- Inoculations occurred 1-5 times weekly for 200 days.
- Control groups received normal brain homogenate or single prion doses.
Main Results:
- Repeated low-dose prion injections led to a high incidence of scrapie.
- Mice receiving single doses of the same prion concentrations did not develop the disease.
- Significant mortality observed in mice with cumulative low-dose prion exposure.
Conclusions:
- Repeated prion exposure, even at low doses, significantly increases the risk of prion disease.
- Cumulative prion dose is a critical factor in disease pathogenesis.
- Findings have implications for understanding iatrogenic CJD transmission.
