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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.(A) tga20 mice were exposed to aerosols generated from 0.1%, 2.5%, 5%, 10% or 20% prion-infected mouse brain homogenates (IBH) for 10 min. (B) Groups of tga20 and (C) CD1 mice were exposed for 1, 5 or 10 min to aerosols generated from a 20% IBH. Experiments were performed twice (different colors). (D) C57BL/6, (E) 129SvxC57BL/6, and Prnpo/o mice were exposed for 10 min to aerosols generated from 20% IBH. Kaplan-Meier curves describe the percentage of survival after particular time points post exposure to prion aerosols (y-axis represents percentage of living mice; x-axis demonstrates survival time in days post inoculation). Different colors and symbols describe the various experimental groups. (F) Jittered scatter plot of survival time against concentration of prion aerosols generated out of IBH with added linear regression fit (p = 0.0622). (G) Jittered scatter plot of survival time against exposure time for tga20 mice with added linear regression fit. The negative correlation between survival time and exposure time is significant (p<0.001***). (H) Consecutive paraffin sections of the right hippocampus of Prnpo/o, tga20, CD1 and C57BL/6 mice stained with HE (for spongiosis, gliosis, neuronal cell loss), SAF84 (PrPSc deposits), GFAP (astrogliosis) and Iba-1 (microglia). All animals had been exposed to aerosols generated from 20% IBH for 10 min. Scale bars: 100µm.
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ppat-1001257-g001: Prion transmission through aerosols.(A) tga20 mice were exposed to aerosols generated from 0.1%, 2.5%, 5%, 10% or 20% prion-infected mouse brain homogenates (IBH) for 10 min. (B) Groups of tga20 and (C) CD1 mice were exposed for 1, 5 or 10 min to aerosols generated from a 20% IBH. Experiments were performed twice (different colors). (D) C57BL/6, (E) 129SvxC57BL/6, and Prnpo/o mice were exposed for 10 min to aerosols generated from 20% IBH. Kaplan-Meier curves describe the percentage of survival after particular time points post exposure to prion aerosols (y-axis represents percentage of living mice; x-axis demonstrates survival time in days post inoculation). Different colors and symbols describe the various experimental groups. (F) Jittered scatter plot of survival time against concentration of prion aerosols generated out of IBH with added linear regression fit (p = 0.0622). (G) Jittered scatter plot of survival time against exposure time for tga20 mice with added linear regression fit. The negative correlation between survival time and exposure time is significant (p<0.001***). (H) Consecutive paraffin sections of the right hippocampus of Prnpo/o, tga20, CD1 and C57BL/6 mice stained with HE (for spongiosis, gliosis, neuronal cell loss), SAF84 (PrPSc deposits), GFAP (astrogliosis) and Iba-1 (microglia). All animals had been exposed to aerosols generated from 20% IBH for 10 min. Scale bars: 100µm.

Mentions: Groups of mice overexpressing PrPC (tga20; n = 4–7) were exposed to prion aerosols derived from infectious or healthy brain homogenates (henceforth IBH and HBH) at various concentrations (0.1, 2.5, 5, 10 and 20%) for 10 min (Fig. 1A, Table 1). All tga20 mice exposed to aerosols derived from IBH (concentration: ≥2.5%) succumbed to scrapie with an attack rate of 100%. The incubation time negatively correlated with the IBH concentration (2.5%: n = 4, 165±54 dpi; 5%: n = 4, 131±7 dpi; 10%: n = 5, 161±27 dpi; 20%: n = 6, 133±8 dpi; p = 0.062, standard linear regression on standard ANOVA; Fig. 1A and F, Table 1, Table S1A).


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.(A) tga20 mice were exposed to aerosols generated from 0.1%, 2.5%, 5%, 10% or 20% prion-infected mouse brain homogenates (IBH) for 10 min. (B) Groups of tga20 and (C) CD1 mice were exposed for 1, 5 or 10 min to aerosols generated from a 20% IBH. Experiments were performed twice (different colors). (D) C57BL/6, (E) 129SvxC57BL/6, and Prnpo/o mice were exposed for 10 min to aerosols generated from 20% IBH. Kaplan-Meier curves describe the percentage of survival after particular time points post exposure to prion aerosols (y-axis represents percentage of living mice; x-axis demonstrates survival time in days post inoculation). Different colors and symbols describe the various experimental groups. (F) Jittered scatter plot of survival time against concentration of prion aerosols generated out of IBH with added linear regression fit (p = 0.0622). (G) Jittered scatter plot of survival time against exposure time for tga20 mice with added linear regression fit. The negative correlation between survival time and exposure time is significant (p<0.001***). (H) Consecutive paraffin sections of the right hippocampus of Prnpo/o, tga20, CD1 and C57BL/6 mice stained with HE (for spongiosis, gliosis, neuronal cell loss), SAF84 (PrPSc deposits), GFAP (astrogliosis) and Iba-1 (microglia). All animals had been exposed to aerosols generated from 20% IBH for 10 min. Scale bars: 100µm.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3020930&req=5

ppat-1001257-g001: Prion transmission through aerosols.(A) tga20 mice were exposed to aerosols generated from 0.1%, 2.5%, 5%, 10% or 20% prion-infected mouse brain homogenates (IBH) for 10 min. (B) Groups of tga20 and (C) CD1 mice were exposed for 1, 5 or 10 min to aerosols generated from a 20% IBH. Experiments were performed twice (different colors). (D) C57BL/6, (E) 129SvxC57BL/6, and Prnpo/o mice were exposed for 10 min to aerosols generated from 20% IBH. Kaplan-Meier curves describe the percentage of survival after particular time points post exposure to prion aerosols (y-axis represents percentage of living mice; x-axis demonstrates survival time in days post inoculation). Different colors and symbols describe the various experimental groups. (F) Jittered scatter plot of survival time against concentration of prion aerosols generated out of IBH with added linear regression fit (p = 0.0622). (G) Jittered scatter plot of survival time against exposure time for tga20 mice with added linear regression fit. The negative correlation between survival time and exposure time is significant (p<0.001***). (H) Consecutive paraffin sections of the right hippocampus of Prnpo/o, tga20, CD1 and C57BL/6 mice stained with HE (for spongiosis, gliosis, neuronal cell loss), SAF84 (PrPSc deposits), GFAP (astrogliosis) and Iba-1 (microglia). All animals had been exposed to aerosols generated from 20% IBH for 10 min. Scale bars: 100µm.
Mentions: Groups of mice overexpressing PrPC (tga20; n = 4–7) were exposed to prion aerosols derived from infectious or healthy brain homogenates (henceforth IBH and HBH) at various concentrations (0.1, 2.5, 5, 10 and 20%) for 10 min (Fig. 1A, Table 1). All tga20 mice exposed to aerosols derived from IBH (concentration: ≥2.5%) succumbed to scrapie with an attack rate of 100%. The incubation time negatively correlated with the IBH concentration (2.5%: n = 4, 165±54 dpi; 5%: n = 4, 131±7 dpi; 10%: n = 5, 161±27 dpi; 20%: n = 6, 133±8 dpi; p = 0.062, standard linear regression on standard ANOVA; Fig. 1A and F, Table 1, Table S1A).

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