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Characterizing the strain and host range properties of prions causing emergent forms of chronic wasting disease

Award Number: R01NS109376
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY / ABSTRACT Our broad, long-term objectives are to understand the fundamental properties and operative mechanisms of infectious prion transmission, and ultimately to prevent unpredictable recurrences of prion epidemics. This application focuses on chronic wasting disease (CWD), a burgeoning, highly contagious cervid prion disease which has attained global epidemic status. Understanding the properties of North American, European, and Asian CWD prions is an important goal of this proposal. We propose three Specific Aims to address our central hypothesis: that the conformationally protean properties of CWD prions results in the evolution of strains with novel host range properties, and unpredictable zoonotic potential. Our Lead Aim seeks to characterize the transmission properties of emergent Norwegian and South Korean CWD prions. It builds upon our preliminary findings that the strain properties of Scandinavian and North American CWD prions are distinct. We will comprehensively assess and compare the transmission properties emergent CWD prions from different geographic locations and species using well characterized transgenic and novel gene-targeted mouse models expressing prion protein (PrP) genes from susceptible species. In Aim II, we will assess the conformational properties of novel CWD strains using innovative ELISA approaches and monoclonal antibodies recognizing defined conformational epitopes. We will assess the properties of CWD strains in cell culture models, and using cell free conversion assays. We will define the amplitude and temporal accumulation of various CWD strains in infected mice by titration in susceptible cells. Finally, using transgenic mouse modeling, we will assess the effects of PrP polymorphisms on strain selection and pathogenesis, and address the susceptibility of at risk species. In our final Aim, we will compare the host-range properties, and zoonotic potential of CWD prions. Our preliminary data describing novel Nor-CWD strains, and the possibility of detecting additional emergent CWD strains, provide additional uncertainty as to whether CWD- exposed humans, or species in contact with wild cervids, are at risk for developing novel prion diseases. We will assess a variety of species barriers by challenging conventional transgenic mouse models expressing PrP from various species including cattle, sheep, and humans, with CWD prions. We will also address the role of CWD adaptation in peripheral tissues on the human species barrier.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = -$1 )
2025	2022	COLORADO STATE UNIVERSITY	601 S HOWES ST	FORT COLLINS	CO	80521	LARIMER	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	11/13/2024	NON-COMPETING CONTINUATION	-$1
														Subtotal = -$1

Issue Date FY: 2022 ( Subtotal = $469,046 )
2022	2022	COLORADO STATE UNIVERSITY	601 S HOWES ST	FORT COLLINS	CO	80521	LARIMER	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	5/16/2022	NON-COMPETING CONTINUATION	$469,046
														Subtotal = $469,046

Issue Date FY: 2021 ( Subtotal = $469,046 )
2021	2021	COLORADO STATE UNIVERSITY	601 S HOWES ST	FORT COLLINS	CO	80521	LARIMER	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	6/17/2021	NON-COMPETING CONTINUATION	$469,046
														Subtotal = $469,046

Issue Date FY: 2020 ( Subtotal = $469,046 )
2020	2020	COLORADO STATE UNIVERSITY	601 S HOWES ST	FORT COLLINS	CO	80521	LARIMER	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	7/2/2020	NON-COMPETING CONTINUATION	$469,046
														Subtotal = $469,046

Issue Date FY: 2019 ( Subtotal = $496,045 )
2019	2019	COLORADO STATE UNIVERSITY	601 S HOWES ST	FORT COLLINS	CO	80521	LARIMER	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	6/24/2019	NON-COMPETING CONTINUATION	$496,045
														Subtotal = $496,045

Issue Date FY: 2018 ( Subtotal = $482,214 )
2018	2018	COLORADO STATE UNIVERSITY	601 S HOWES ST	FORT COLLINS	CO	80521	LARIMER	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	9/20/2018	NEW	$482,214
														Subtotal = $482,214

Grand Total All Awards = $2,385,396

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Characterizing the strain and host range properties of prions causing emergent forms of chronic wasting disease

Award Number: R01NS109376

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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