# The role of structural plasticity in the norovirus capsid

> **NIH NIH R01** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2020 · $559,337

## Abstract

Project Summary/Abstract
 Animal viruses share two important features; a) an efficient system for delivering their genome to the target
cell usually involving an activation process in the virion and b) a means of interacting with the adaptive immune
system of the host. The structural and biophysical studies detailed here will show how the noroviruses have
evolved capsids that perform both functions.
 Human noroviruses are responsible for almost a fifth of all cases of gastroenteritis worldwide. Noroviruses
generate new strains every 2-4 years that cause worldwide epidemics. In the US alone, annually there are ~20
million cases and more than 70,000 hospitalizations of children. Efforts for a vaccine have been hindered by a
lack of detailed structural information about antibody binding and the mechanisms of antibody escape. In
addition, containment of the disease is also problematic since as few as ten virions are sufficient to infect a
normal adult. Understanding all of these processes has been difficult with human noroviruses because of the
lack of a tissue culture system and small animal model. To this end, we will be using the highly tractable
mouse norovirus system where we have a cell culture system and an infectious clone.
 With regard to the first function of a viral capsid, we present evidence that noroviruses appear to undergo
an apparent activation process where the addition of bile salts causes the protruding domain (P domain) to
rotated and move ~16Å onto the surface of the shell. This movement is correlated with greatly enhanced
binding of the virus to the cell. In terms of the second function of a viral capsid, we also present evidence that
the P domain itself is highly plastic and that this motility plays an integral role in receptor binding and antibody
escape. Therefore, the studies presented here will not only elucidate a very unique norovirus activation
process, but also how the virus evades the immune system. Together, this information could be leveraged in
the future to develop vaccines and therapeutics for this serious disease.

## Key facts

- **NIH application ID:** 9857553
- **Project number:** 5R01AI141465-02
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** Bernard MONTGOMERY PETTITT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $559,337
- **Award type:** 5
- **Project period:** 2019-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9857553

## Citation

> US National Institutes of Health, RePORTER application 9857553, The role of structural plasticity in the norovirus capsid (5R01AI141465-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9857553. Licensed CC0.

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