# Project 2

> **NIH NIH P01** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2022 · $429,351

## Abstract

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.

## Key facts

- **NIH application ID:** 10332508
- **Project number:** 2P01AI077774-11
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** CLAUDIO SOTO
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $429,351
- **Award type:** 2
- **Project period:** 2008-08-15 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10332508

## Citation

> US National Institutes of Health, RePORTER application 10332508, Project 2 (2P01AI077774-11). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10332508. Licensed CC0.

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