# Viruses Hijack Innate Immune Peptides to Enhance Infection

> **NIH NIH F32** · UNIVERSITY OF WASHINGTON · 2024 · $74,284

## Abstract

Project Summary/Abstract
Defensins are small, innate immune peptides with broad antimicrobial activity, yet some pathogens, including
non-enveloped viruses, have evolved methods to evade or co-opt defensins to enhance their infectivity.
Resistance or enhancement is most pronounced for enteric viruses, leading to the hypothesis that fecal/oral
transmission facilitates viral evolution to escape defensin neutralization. The studies herein will determine the
molecular, cellular, and evolutionary mechanisms of viral escape from defensin action. Using a library of
chimeric defensin peptides, we will determine the structural and biochemical properties of defensins essential
to their activity against human adenovirus, rotavirus, and human papillomavirus (Aim1). Testing defensins
against representatives from multiple viral families will provide insight into which defensin structural elements
are globally required for activity, versus which are pathogen-specific. To more clearly elucidate the drivers of
viral resistance to defensins, we will leverage the biological diversity across enteroviruses (EVs) to study how
defensin sensitivity is related to viral transmission (Aim 2). In parallel, we will determine the cellular mechanism
of EV neutralization by defensins, as well as the mechanism of EV defensin escape (Aim 3). This work will
provide insight into how viral pathogens bypass the host innate immune system to promote infectivity,
expanding our understanding of the host/pathogen evolutionary arms race. Many of the viruses included in
these studies cause serious human illnesses, and this work will also point to new routes for antiviral
development.
The proposed work is designed to provide training in several techniques of virology and cellular biology,
including cell culture and viral assays; high-performance liquid chromatography and peptide purification;
biophysical binding assays; cellular mechanism studies; as well as microscopy. In addition to scientific
expertise, the proposed training plan also includes education in scientific communication; mentorship;
responsible research conduct; diversity, equity, and inclusion; as well as a career development plan for
becoming a successful independent researcher. This work will be conducted in the University of Washington
Microbiology Department, which is a hub for infectious disease research. This richly collaborative environment
includes several faculty members and core facilities that provide the necessary resources, equipment, and
expertise to enable completion of the proposed training plan.

## Key facts

- **NIH application ID:** 10899264
- **Project number:** 1F32AI178920-01A1
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Kaitlin Rose Hulce
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $74,284
- **Award type:** 1
- **Project period:** 2024-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10899264

## Citation

> US National Institutes of Health, RePORTER application 10899264, Viruses Hijack Innate Immune Peptides to Enhance Infection (1F32AI178920-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10899264. Licensed CC0.

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