# Functions of the reovirus capsid

> **NIH NIH R01** · TRUSTEES OF INDIANA UNIVERSITY · 2022 · $377,291

## Abstract

The proposed research uses mammalian reovirus (MRV) to define how a single capsid protein, μ1,
influences distinct functions of the viral capsid. MRV particles are comprised of two concentric protein
shells, the outer capsid and the inner core. The μ1 protein is a major component of the outer capsid.
Published evidence and our preliminary data indicate that μ1 performs at least three functions. First,
even though the two proteins are not in physical contact, properties of μ1 influence virus assembly in
a way that alters the presentation of the sigma1 attachment protein on the virion. Second, two μ1
peptides, generated during virus disassembly, cooperate with host lipid membranes to facilitate
further uncoating of the virus and permeabilize host membranes. Third, μ1 influences inter-particle
interactions to form multivirion infectious units. With the aid of the following three Aims, the proposed
research seeks to provide insight into the functions of μ1. In Aim 1, the role of μ1 in maintaining
assembly fidelity will be determined. The position of sigma1 on the particle will be determined by
biochemical studies and cryoelectron microscopy. The contribution of altering the strength of
interaction between μ1 and adjacent capsid proteins on the presentation of sigma1 will be evaluated using
genetic analysis. How changes to sigma1 encapsidation and sigma1 conformation influence virus replication in
vivo will be determined using a mouse model of viral disease. In Aim 2, the function of μ1 in
delivering core particles into the host cytoplasm will be defined. How μ1 peptides recruit entry
intermediates to membranes will be determined by biochemical and genetic studies. The minimal
number of μ1 peptides needed for successful recruitment of a virus entry intermediate, for pore
formation and for successful infection will be quantified. The structure of the virus entry intermediate
associated with the membrane will be determined by cryoelectron microscopy. Host proteins that
associate with capsids following disassembly and influence the efficiency of infection will be identified
by affinity purification and mass spectrometry. In Aim 3, the contribution of μ1 to MVIU formation will
be identified. Regions important for inter-particle interactions will be determined by limited proteolysis
and mass spectrometry. The relationship between MVIU formation, coinfection efficiency, and
reassortment frequency will be determined. Whether MVIU formation also determines reassortment in
vivo and if the determinants of MVIU formation and those that influence the recovery of reassortant
progeny correlate, will be determined. Completion of this work will provide comprehensive insight into
how μ1 completes each of these functions and define the properties of μ1 that influence the capacity
of MRV to replicate in cell culture, produce reassortant progeny, and elicit disease.

## Key facts

- **NIH application ID:** 10328503
- **Project number:** 5R01AI110637-08
- **Recipient organization:** TRUSTEES OF INDIANA UNIVERSITY
- **Principal Investigator:** Pranav Danthi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $377,291
- **Award type:** 5
- **Project period:** 2014-08-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10328503

## Citation

> US National Institutes of Health, RePORTER application 10328503, Functions of the reovirus capsid (5R01AI110637-08). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10328503. Licensed CC0.

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