# Structural, mechanistic, and antigenic insights into the human astrovirus capsid

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA SANTA CRUZ · 2021 · $73,446

## Abstract

PROJECT SUMMARY
Human astroviruses (HAstV) are a leading cause of viral diarrhea in children. Divergent HAstV strains are
associated with fatal human encephalitis. Currently, no vaccines or antiviral therapies exist for HAstV
infections. Our goal is to identify sites of vulnerability (Achilles' heels) on the HAstV surface that can be
exploited for the development of preventative and therapeutic strategies against HAstV. The HAstV virion is a
small, icosahedral virus composed of an RNA genome surrounded by capsid protein. Despite the important
role of the HAstV capsid protein in virus entry into host cells, the location of antibody epitopes and the
mechanisms of virus-neutralizing antibodies are unknown. Our central hypothesis is that the HAstV capsid
spike domain plays a key role in virus entry and is a target of HAstV-neutralizing antibodies. Using a diverse
toolbox of structural, biochemical, immunological, and virological approaches, we will pursue three specific
aims to (1) use structural and biophysical studies to define HAstV capsid epitopes and serotype-reactivity of a
panel of six neutralizing monoclonal antibodies, (2) determine neutralizing mechanisms of a panel of
neutralizing monoclonal antibodies targeting the HAstV capsid spike, and define the role of the HAstV capsid
spike in cell entry, and (3) determine the structures of the divergent, neurotropic HAstV-VA1 capsid core and
spike, test their abilities to elicit neutralizing antibodies, and define HAstV-VA1 neutralizing epitopes. This work
represents the first molecular study of HAstV neutralizing epitopes. Results obtained by this work will elucidate
mechanisms of HAstV entry and neutralization and provide a foundation for the design of vaccines and
therapeutics to prevent and treat HAstV infections.

## Key facts

- **NIH application ID:** 10113465
- **Project number:** 3R01AI144090-03S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA SANTA CRUZ
- **Principal Investigator:** Rebecca Michelle DuBois
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $73,446
- **Award type:** 3
- **Project period:** 2021-03-09 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10113465

## Citation

> US National Institutes of Health, RePORTER application 10113465, Structural, mechanistic, and antigenic insights into the human astrovirus capsid (3R01AI144090-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10113465. Licensed CC0.

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