# Defining defensin-mediated inhibitionand enhancement of rotavirus infection

> **NIH NIH F30** · UNIVERSITY OF WASHINGTON · 2020 · $40,414

## Abstract

ABSTRACT
Rotavirus infection is a prominent global health concern, causing severe gastroenteritis and infecting nearly
every child worldwide by the age of five, despite the currently available vaccines. As a gastrointestinal pathogen,
rotavirus primarily infects mature enterocytes in the small intestine where they face a variety of different immune
responses mounted by the host. One of these host defense mechanisms is the secretion of antimicrobial
peptides. Specifically, our lab is interested in one group of these potent antimicrobial peptides called defensins.
Defensins have well-characterized broad antimicrobial activity. We and others have shown that a-defensins can
function by multiple mechanisms to neutralize viral infection. Despite this potent antiviral activity, certain viruses
can escape or even exhibit enhanced infection in the presence of defensins. One of these viruses is rotavirus.
This proposal seeks to determine the exact nature of how rotaviruses have adapted to host defensins to evade
neutralization during initial infection and, in some instances, usurp this host defense factor and facilitate infection.
I hypothesize that rotavirus exploits the presence of enteric a-defensins during initial infection to
enhance cell entry. Aim 1 will establish the specificity of rotavirus adaptation to the presence of a-defensins
during infection by testing the effects of homologous (species specific) and heterologous (cross-species) a-
defensins on rotavirus infection from 3 different species. Aim 2 will determine the effect that defensins have on
rotavirus binding to the cells using fluorescently labeled virus. Aim 3 will define the molecular basis for interaction
between a-defensins and rotavirus using an experimental evolution approach and deep genome sequencing to
identify regions in rotavirus that are important for interaction with defensin. These findings will be further explored
using the novel rotavirus reverse-genetics system. The idea of defensin-mediated enhancement of viral infection
is an important component to understanding innate immune system interactions with pathogens. Together these
three aims could inform the importance of host factors that contribute to the worldwide burden of diarrheal
disease.

## Key facts

- **NIH application ID:** 10074128
- **Project number:** 5F30AI140620-02
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** KARINA DIAZ-DAVIS
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $40,414
- **Award type:** 5
- **Project period:** 2019-09-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10074128

## Citation

> US National Institutes of Health, RePORTER application 10074128, Defining defensin-mediated inhibitionand enhancement of rotavirus infection (5F30AI140620-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10074128. Licensed CC0.

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