# Mechanisms of Prion Transmission, Evolution and Adaptation

> **NIH NIH P01** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2020 · $557,415

## Abstract

Project Summary / Abstract
Our broad, long-term objectives are to understand the fundamental properties and operative mechanisms of
infectious prion transmission in animals and humans; how properties change during this process; and whether
evolution allows infection of additional species. Aim 1 explores an underappreciated but important
phenomenon. When prions infect a new species, despite replicating they unexpectedly cause no disease, but
maintain the ability to kill the original species. We will quantify how much and when such prion replication
occurs, and define biochemical and biological properties differentiating these from conventional prions. Aim 2
will address the related issue of how prion strains are propagated, and how prions manifest dominant and
recessive traits. Unlike viral characteristics that are genetically controlled, prions, which lack nucleic acids must
employ a different mechanism. We find that dominant and recessive prion traits are controlled at the level of
protein-protein interactions. We will monitor molecular events in this process using an innovative approach
involving antibodies that discriminate subtle prion differences, in much the same way that geneticists
discriminate the actions of alternative genes during disease. In Aim 3, we will use a powerful new mouse
model that recapitulates important aspects of chronic wasting disease (CWD), an emerging epidemic of deer,
elk and moose. These mice enable us to study aspects of CWD that account for its uniquely contagious
transmission. All three aims employ powerful and innovative approaches including uniquely suited genetically
modified mice, cell culture assays, cell-free amplification, and antibodies that distinguish prion variants. These
aims address basic, unresolved issues about how prions function which is important because prion diseases
occur as unpredictable epidemics (e.g. mad cow disease), are lethal, and currently incurable. CWD is the only
known prion disorder affecting wild animals. Its efficient contagious transmission means that it is rapidly
increasing in geographic range. Also CWD continues to affect new cervid (antler-bearing) species. Whether
CWD or its evolving forms will spread to other species, or to humans, as was the case for mad cow disease, is
currently unknown but of significant importance to public health.

## Key facts

- **NIH application ID:** 9920663
- **Project number:** 5P01AI077774-10
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Glenn C Telling
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $557,415
- **Award type:** 5
- **Project period:** — → 2022-03-10

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9920663

## Citation

> US National Institutes of Health, RePORTER application 9920663, Mechanisms of Prion Transmission, Evolution and Adaptation (5P01AI077774-10). Retrieved via AI Analytics 2026-06-10 from https://api.ai-analytics.org/grant/nih/9920663. Licensed CC0.

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