# A functional evolutionary genetic approach to combat viral infection

> **NIH NIH DP1** · UT SOUTHWESTERN MEDICAL CENTER · 2024 · $1,148,000

## Abstract

Project Summary
Humans are under increasing threat from viruses that spill over from animal reservoirs. Most of
these viral diseases lack targeted treatments. We speculate that this unmet medical need might
be addressable by first understanding the evolutionary principles underlying antiviral immune
responses. A major component of innate immunity in mammals is the interferon response.
Interferon induces hundreds of genes, many of which encode effector proteins that suppress
viral infection. In mammals, these antiviral effectors are rapidly evolving, most likely in
response to the genetic "arms race" continually occurring between virus and host. Further,
certain mammalian orders, such as primates, rodents, bats, and carnivores, are particularly rich
in viruses that have the potential to spill over into humans. We hypothesize that the genomes of
these viral zoonotic reservoirs encode unique antiviral effectors that may be harnessed to
combat human viral pathogens. The goals of this project are to identify, characterize, and
validate the efficacy of novel antiviral proteins from diverse non-model mammalian species.
State-of-the-art genetic screening platforms will be used to discover antiviral genes in primary
cell cultures obtained from multiples species in the following mammalian orders: Primate,
Rodentia, Chiroptera, and Carnivora. Validated effectors will be characterized mechanistically
with a suite of virological, biochemical, molecular, and cell biological approaches. The potential
for these effectors to suppress human viruses will be tested in murine models of human viral
disease. Outcomes will include the creation of the first comprehensive Mammalian Antiviral
Protein Atlas, the discovery of new genetically-encoded antiviral mechanisms, and proof-of-
concept that human viral disease can be thwarted by naturally occurring proteins from other
species. The impact of this proposal will be the development of a new area of biomedical
research at the intersection of virology, immunology, and evolutionary biology. Long term
prospects include harnessing the results of these studies to inspire alternative approaches to
antiviral drug development.

## Key facts

- **NIH application ID:** 10891465
- **Project number:** 5DP1AI158124-05
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** John W. Schoggins
- **Activity code:** DP1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,148,000
- **Award type:** 5
- **Project period:** 2020-09-30 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10891465

## Citation

> US National Institutes of Health, RePORTER application 10891465, A functional evolutionary genetic approach to combat viral infection (5DP1AI158124-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10891465. Licensed CC0.

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