# The effect of extracellular vesicle-mediated transmission on reovirus infection

> **NIH NIH F31** · VANDERBILT UNIVERSITY · 2022 · $31,986

## Abstract

PROJECT SUMMARY
The traditional idea that non-enveloped viruses exit cells via lysis is being challenged with recent studies showing
that many virus families utilize extracellular vesicles (EVs) for non-lytic egress. EV-mediated transmission can
enable viral immune evasion and collective particle transmission to potentially enhance productive infection. The
egress mechanisms of mammalian orthoreovirus (reovirus), a member of the Reoviridae virus family that causes
significant disease in a broad range of human and animal hosts, remain largely understudied. Rotavirus, another
member of the Reoviridae family, was recently reported to egress from host cells in large EVs. EV containment
enhanced rotavirus virulence in vivo. The goal of my proposed research is to understand mechanisms of reovirus
egress and to elucidate how the mode of reovirus transmission affects reovirus infection. Using different types
of cultured cells and genetically barcoded reovirus, my preliminary work indicates that i) reovirus particles can
egress in large EVs, ii) EV-mediated reovirus egress is virus strain- and cell type-dependent, iii) EV containment
protects reovirus particles from antibody-mediated neutralization, and iv) EV-mediated transmission increases
the frequency of multiparticle infection compared to free reovirus. I hypothesize that EV-mediated reovirus egress
is dependent on viral interaction with the host cell, promotes multiparticle infection, and enhances replication
kinetics. To test this hypothesis, I propose two specific aims. In Specific Aim 1, I will use immunoblotting,
electron microscopy, and genetically engineered reovirus to define the properties of reovirus-associated EV
populations and identify reovirus determinants of cell type-dependent EV-mediated egress. In Specific Aim 2, I
will use genetically barcoded reovirus, plaque assays, and RT-qPCR to identify the effects of extracellular
vesicle-mediated transmission on reovirus entry, multiparticle infection, and replication kinetics. The findings
elucidated by the proposed aims will likely reveal a novel mechanism of host cell-assisted, nonlytic reovirus
egress, which may apply to other viruses of the Reoviridae family. Continued studies building on these findings
will illuminate the impact of transmission mode on reovirus virulence and dissemination within a host organism.

## Key facts

- **NIH application ID:** 10387888
- **Project number:** 1F31AI167541-01
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Sydni Caet Smith
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $31,986
- **Award type:** 1
- **Project period:** 2022-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10387888

## Citation

> US National Institutes of Health, RePORTER application 10387888, The effect of extracellular vesicle-mediated transmission on reovirus infection (1F31AI167541-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10387888. Licensed CC0.

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