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Aerosols transmit prions to immunocompetent and immunodeficient mice.

Haybaeck J, Heikenwalder M, Klevenz B, Schwarz P, Margalith I, Bridel C, Mertz K, Zirdum E, Petsch B, Fuchs TJ, Stitz L, Aguzzi A - PLoS Pathog. (2011)

Bottom Line: However, prions are not generally considered to be airborne.We conclude that aerogenic exposure to prions is very efficacious and can lead to direct invasion of neural pathways without an obligatory replicative phase in lymphoid organs.This previously unappreciated risk for airborne prion transmission may warrant re-thinking on prion biosafety guidelines in research and diagnostic laboratories.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Institute of Neuropathology, University Hospital Zurich, Zurich, Switzerland.

ABSTRACT
Prions, the agents causing transmissible spongiform encephalopathies, colonize the brain of hosts after oral, parenteral, intralingual, or even transdermal uptake. However, prions are not generally considered to be airborne. Here we report that inbred and crossbred wild-type mice, as well as tga20 transgenic mice overexpressing PrP(C), efficiently develop scrapie upon exposure to aerosolized prions. NSE-PrP transgenic mice, which express PrP(C) selectively in neurons, were also susceptible to airborne prions. Aerogenic infection occurred also in mice lacking B- and T-lymphocytes, NK-cells, follicular dendritic cells or complement components. Brains of diseased mice contained PrP(Sc) and transmitted scrapie when inoculated into further mice. We conclude that aerogenic exposure to prions is very efficacious and can lead to direct invasion of neural pathways without an obligatory replicative phase in lymphoid organs. This previously unappreciated risk for airborne prion transmission may warrant re-thinking on prion biosafety guidelines in research and diagnostic laboratories.

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Prion transmission through aerosols in complement-deficient and newborn mice.(A) C3C4−/− mice and (B) newborn tga20 and CD1 mice were exposed for 10 min to a 20% aerosolized IBH. Survival curves (right panels) as well as histological and immunohistochemical characterization of hippocampi indicate that all prion-exposed mice developed scrapie efficiently. Scale bars: 100µm.
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ppat-1001257-g004: Prion transmission through aerosols in complement-deficient and newborn mice.(A) C3C4−/− mice and (B) newborn tga20 and CD1 mice were exposed for 10 min to a 20% aerosolized IBH. Survival curves (right panels) as well as histological and immunohistochemical characterization of hippocampi indicate that all prion-exposed mice developed scrapie efficiently. Scale bars: 100µm.

Mentions: Certain components of the complement system (e.g. C3; C1qa) play an important role in early prion uptake, peripheral prion replication and neuroinvasion after peripheral prion challenge [43], [55], [56]. We have tested whether this is true also for exposure to prion aerosols. Mice lacking both complement components C3 and C4 (C3C4−/−) were exposed for 10 min to 20% aerosolized IBH. All C3C4−/− mice succumbed to scrapie (n = 3, 382±33 dpi; Fig. 4A). Histopathological evaluation of all scrapie affected mice revealed astrogliosis, spongiform changes and PrP-deposition in the CNS (Fig. 4A).


Aerosols transmit prions to immunocompetent and immunodeficient mice.

Haybaeck J, Heikenwalder M, Klevenz B, Schwarz P, Margalith I, Bridel C, Mertz K, Zirdum E, Petsch B, Fuchs TJ, Stitz L, Aguzzi A - PLoS Pathog. (2011)

Prion transmission through aerosols in complement-deficient and newborn mice.(A) C3C4−/− mice and (B) newborn tga20 and CD1 mice were exposed for 10 min to a 20% aerosolized IBH. Survival curves (right panels) as well as histological and immunohistochemical characterization of hippocampi indicate that all prion-exposed mice developed scrapie efficiently. Scale bars: 100µm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3020930&req=5

ppat-1001257-g004: Prion transmission through aerosols in complement-deficient and newborn mice.(A) C3C4−/− mice and (B) newborn tga20 and CD1 mice were exposed for 10 min to a 20% aerosolized IBH. Survival curves (right panels) as well as histological and immunohistochemical characterization of hippocampi indicate that all prion-exposed mice developed scrapie efficiently. Scale bars: 100µm.
Mentions: Certain components of the complement system (e.g. C3; C1qa) play an important role in early prion uptake, peripheral prion replication and neuroinvasion after peripheral prion challenge [43], [55], [56]. We have tested whether this is true also for exposure to prion aerosols. Mice lacking both complement components C3 and C4 (C3C4−/−) were exposed for 10 min to 20% aerosolized IBH. All C3C4−/− mice succumbed to scrapie (n = 3, 382±33 dpi; Fig. 4A). Histopathological evaluation of all scrapie affected mice revealed astrogliosis, spongiform changes and PrP-deposition in the CNS (Fig. 4A).

Bottom Line: However, prions are not generally considered to be airborne.We conclude that aerogenic exposure to prions is very efficacious and can lead to direct invasion of neural pathways without an obligatory replicative phase in lymphoid organs.This previously unappreciated risk for airborne prion transmission may warrant re-thinking on prion biosafety guidelines in research and diagnostic laboratories.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Institute of Neuropathology, University Hospital Zurich, Zurich, Switzerland.

ABSTRACT
Prions, the agents causing transmissible spongiform encephalopathies, colonize the brain of hosts after oral, parenteral, intralingual, or even transdermal uptake. However, prions are not generally considered to be airborne. Here we report that inbred and crossbred wild-type mice, as well as tga20 transgenic mice overexpressing PrP(C), efficiently develop scrapie upon exposure to aerosolized prions. NSE-PrP transgenic mice, which express PrP(C) selectively in neurons, were also susceptible to airborne prions. Aerogenic infection occurred also in mice lacking B- and T-lymphocytes, NK-cells, follicular dendritic cells or complement components. Brains of diseased mice contained PrP(Sc) and transmitted scrapie when inoculated into further mice. We conclude that aerogenic exposure to prions is very efficacious and can lead to direct invasion of neural pathways without an obligatory replicative phase in lymphoid organs. This previously unappreciated risk for airborne prion transmission may warrant re-thinking on prion biosafety guidelines in research and diagnostic laboratories.

Show MeSH
Related in: MedlinePlus