# Mechanisms of Reovirus Bloodstream Dissemination

> **NIH NIH R01** · UNIV OF ARKANSAS FOR MED SCIS · 2020 · $364,007

## Abstract

PROJECT SUMMARY
 Viral spread from the mucosal sites of infection to target tissues and organs is a
fundamental step in the pathogenesis of many viral diseases. Viruses typically use the
bloodstream and lymphatic system as the pathway for delivering virus to organs and tissues
throughout the body. Although general principles of lymphatic-hematogenous viral spread are
understood, little is known about the viral and cellular determinants that govern virus
dissemination by these routes. The overall objective of experiments described in this application
is to define mechanisms and functional consequences of viral spread via the blood. Work
proposed in this application seeks determine how mammalian orthoreovirus (reovirus) traffics
from an initial site of inoculation to the bloodstream. Previous studies revealed that nonstructural
protein σ1s is required for reovirus spread by hematogenous routes. New preliminary data
indicates that σ1s functions to enhance reovirus protein synthesis, which allows reovirus to
replicate efficiently in the presence of an IFN response in cell types that provide access to the
vasculature. Together, these data indicate that σ1s-mediated inactivation of host IFN responses
allows reovirus to overcome cellular barriers that restrict access to the bloodstream. Based on
preliminary studies, experiments in Specific Aim 1 will define cell types required to disseminate
reovirus from the site of inoculation to the bloodstream. Experiments in Specific Aim 2 will define
mechanisms by which σ1s promotes reovirus protein synthesis. Experiments proposed in
Specific Aim 3 will examine how reovirus bloodstream spread contributes to viral clearance from
the central nervous system. These experiments will use a combination of powerful mouse and
reovirus genetics systems to address how reovirus gains access to the blood. This research will
have broad general impact in uncovering unifying principles that govern systemic viral spread.

## Key facts

- **NIH application ID:** 9986642
- **Project number:** 5R01AI118801-05
- **Recipient organization:** UNIV OF ARKANSAS FOR MED SCIS
- **Principal Investigator:** Karl W Boehme
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $364,007
- **Award type:** 5
- **Project period:** 2016-09-21 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9986642

## Citation

> US National Institutes of Health, RePORTER application 9986642, Mechanisms of Reovirus Bloodstream Dissemination (5R01AI118801-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9986642. Licensed CC0.

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