Chronic Wasting Disease: Pathogenesis, Transmission and Detection of Zoonotic Prion Diseases Project Number 5P01AI077774-14 2025

Pathogenesis, Transmission and Detection of Zoonotic Prion Diseases Project Number 5P01AI077774-14 2025

Pathogenesis, Transmission and Detection of Zoonotic Prion Diseases

Project Number5P01AI077774-14

Former Number3P01AI077774-09W1

Contact PI/Project LeaderSOTO, CLAUDIO

Awardee Organization

Description

Abstract Text

ABSTRACT Prion diseases are a group of infectious neurodegenerative disorders affecting humans and other mammals, which are transmitted by an unconventional proteinaceous infectious agent termed prion. CWD is so far the only prion disease of wild animals; it is highly contagious and the exact origin, prevalence, and mechanisms of transmission remain incompletely understood. The progressive increase of CWD prevalence in the USA has likely resulted in a substantial contamination of the environment with infectious prions and may lead to new prion diseases in animals that share the habitat of cervids. The disease has been rapidly expanding geographically and now affects 27 states in USA, three Canadian provinces, South Korea and Northern Europe, including Norway, Sweden and Finland. The risk of transmission of CWD to other animal species or to humans is unknown and surveillance methods to detect the infection in non-cervid species are limited. This Program Project has received continuous funding for the past 11 years, which has enabled us to implement a large and complementary set of unique techniques, model systems, reagents, personnel and expertise crucial to understand the CWD problem. In the last competitive review, we received a perfect score of 10 and reviewers identified many strengths and “not any significant weakness”. The progress during this cycle has been stellar, with many important discoveries and 118 high profile publications. The main goal of this iteration of the Program Project will be to study the molecular and cellular mechanisms responsible for prion replication and prion strain diversity in CWD. We will study the generation, mutation and evolution of CWD prion strains, the inter-species transmission potential of CWD (with particular focus on its zoonotic potential) and the role of the environment on CWD transmission. This Program Project aims to address some of the most important questions in CWD research, including the possibly origin of CWD, the mechanism and routes of transmission of the disease among animals, the natural strain diversity of CWD, the atomic resolution structure of infectious prions, the evaluation of the zoonotic potential of CWD, the factors controlling the cervid/human species barrier, the role of the environment on prion transmission and the development of efficient procedures to detect infectious CWD prions. To achieve these goals, this Program Project assembles a group of highly accomplished scientists in the prion field, particularly experts on CWD transmission, who have access to the relevant models, techniques, samples, resources and expertise to provide a complementary and comprehensive investigation of the problem.

Public Health Relevance Statement

NARRATIVE This is a competing renewal application of a very successful Program Project Grant that has received continued funding for the past 11 years. During this time we have maintained a strong productivity, we have built a very collaborative and synergistic team and we have implemented substantial expertise and resources to study Chronic Wasting Disease (CWD), a prion disorder that continue to spread uncontrollably among cervids in USA. In this project, we will investigate the mechanism of CWD prion replication and the generation, adaptation and evolution of prion strains, the atomic resolution structure of infectious prions, the routes of transmission of the disease among animals, the evaluation of the zoonotic potential of CWD, the role of the environment on prion transmission and the development of efficient procedures to detect the infectious agent.

NIH Spending Category

No NIH Spending Category available.

Details

Contact PI/ Project Leader

Name

SOTO, CLAUDIO

Title

PROFESSOR AND DIRECTOR

Contact

Other PIs

Not Applicable

Program Official

Name

ALARCON, RODOLFO M

Contact

Organization

Name

UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON

City

HOUSTON

Country

UNITED STATES (US)

Department Type

NEUROLOGY

Organization Type

SCHOOLS OF MEDICINE

State Code

Congressional District

Other Information

Opportunity Number

PAR-20-072

Study Section

ZAI1-ESB-M(S2)

Fiscal Year

2025

Award Notice Date

07-April-2025

Administering Institutes or Centers

National Institute of Allergy and Infectious Diseases

Assistance Listing Number

93.855

DUNS Number

800771594

UEI

ZUFBNVZ587D4

Project Start Date

15-August-2008

Project End Date

28-February-2027

Budget Start Date

01-March-2025

Budget End Date

28-February-2026

No Cost Extension

Project Funding Information for 2025

Total Funding

$2,528,112

Direct Costs

$2,221,754

Indirect Costs

$306,358

Year	Funding IC	FY Total Cost by IC
2025	National Institute of Allergy and Infectious Diseases	$2,528,112

Project 2

Parent Project Number5P01AI077774-14

Sub-Project ID5511

Contact PI/Project LeaderSOTO, CLAUDIO

Awardee Organization

Description

Abstract Text

ABSTRACT Chronic wasting disease (CWD) affecting various species of cervids in North American and Northern Europe represents a serious problem, because it continues to propagate uncontrollably among wild and captive cervids. CWD appears to be very heterogeneous with multiple different strains and can be transmitted to other animal species. The risk of CWD transmission to humans is unknown which is a major concern because the number of sick animals and their geographical distribution is rapidly increasing. The mechanism by which CWD propagates so efficiently among cervids is also unknown. The main goal of this project is to utilize a set of highly innovative techniques to study the cellular, molecular and structural features of naturally occurring CWD strains and their potential for inter- species transmission, particularly focusing on the possibility that certain CWD strains may infect humans. We will also attempt to elucidate the atomic resolution structure of CWD prions using cryo-electron microscopy. The overarching hypothesis is that CWD exists as multiple strains in distinct individuals and even within the same individual in different brain cells and that inter- species transmission and zoonotic potential depend on the specific strain characteristics. The project is divided in the following specific aims: (1) Study the structural and molecular diversity of natural CWD strains and the high resolution three-dimensional structure of CWD prions. (2) Understand CWD prion strain diversity in single brain cells isolated by laser capture microdissection and subsequently amplified by PMCA. (3) Evaluate CWD inter-species transmission spillover potential and its effect on zoonotic potential. (4) Analyze the deer-human prion species barrier in vivo using chimeric mice harboring human and cervid neuronal cells. The studies included in this projects will address some of the most pressing questions regarding CWD, including (i) the CWD prion strain variability, (ii) the zoonotic potential of different CWD prion strains, (iii) the atomic resolution structure of infectious prions and the structural basis of prion strains, (iv) the cellular distribution of CWD prion strains in the brain and its gene expression consequences, (v) the spillover potential of CWD to other animal species, (vi) the potential role of intermediate species in the transmission of CWD prions to humans. The findings generated in this project will be essential to design measures to prevent further propagation of CWD, and to avoid the emergence of new diseases with potentially disastrous consequences.

Public Health Relevance Statement

Data not available.

NIH Spending Category

No NIH Spending Category available.

Details

Contact PI/ Project Leader

Name

SOTO, CLAUDIO

Title

PROFESSOR AND DIRECTOR

Contact

Other PIs

Not Applicable

Program Official

Name

Contact

Email not available

Organization

Name

UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON

City

HOUSTON

Country

UNITED STATES (US)

Department Type

Unavailable

Organization Type

Domestic Higher Education

State Code

Congressional District

Other Information

Opportunity Number

PAR-20-072

Study Section

ZAI1-ESB-M

Fiscal Year

2025

Award Notice Date

07-April-2025

Administering Institutes or Centers

National Institute of Allergy and Infectious Diseases

Assistance Listing Number

DUNS Number

800771594

UEI

ZUFBNVZ587D4

Project Start Date

15-August-2008

Project End Date

28-February-2027

Budget Start Date

01-March-2025

Budget End Date

28-February-2026

No Cost Extension

Project Funding Information for 2025

Total Funding

$468,116

Direct Costs

$411,390

Indirect Costs

$56,726

Year	Funding IC	FY Total Cost by IC
2025	National Institute of Allergy and Infectious Diseases	$468,116

Project 3B: Pathogenesis Transmission and Detection of Zoonotic Prion Diseases 5P01AI077774-145513

BARTZ, JASON C

UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON2025NIAID

$331,126

Project 3A: CWD Prion Shedding and Environmental Contamination: Role in Transmission and Zoonotic 5P01AI077774-145512

HOOVER, EDWARD ARTHUR