# Bacterial-mediated enhancement of Coxsackievirus

> **NIH NIH R01** · INDIANA UNIVERSITY INDIANAPOLIS · 2022 · $476,554

## Abstract

Project Summary
Coxsackievirus is a common infection that causes viral myocarditis, meningoencephalitis, and hand, foot, and
mouth disease in children and adults. Coxsackievirus is transmitted by the fecal-oral route and initiates infection
in the gastrointestinal tract. Currently, there is a lack of effective prevention and treatment options for
Coxsackievirus infections. Using a mouse model, recent data demonstrate that Coxsackievirus B3 (CVB3)
utilizes bacteria to aid viral replication and pathogenesis in vivo. However, the mechanism for this observation is
unclear. In preliminary data, we have demonstrated that bacteria can enhance CVB3 infectivity and
thermostability in vitro. We also found that Gram-negative Salmonella enterica binds to CVB3 and can enhance
infectivity and stability of CVB3 while Escherichia coli does not. We also found that structures in the major cell
wall component of Salmonella, lipopolysaccharide (LPS), can impact viral stability. These data suggest that
specific bacteria and bacterial cell wall components are required to enhance CVB3. Therefore, this study aims
to elucidate the bacterial structure and site of binding to CVB3, and investigate the mechanisms by which bacteria
aid viral thermostability. This goal will be accomplished in three aims. In Aim 1, we will determine the bacterial
cell wall components that interact with CVB3. Using Salmonella LPS mutants, we will characterize the critical
elements of LPS required to interact with CVB3. In Aim 2, we will identify the virion binding site between bacteria
and Coxsackievirus. Using a combination of state-of-the-art cryogenic electron microscopy and CVB3 mutants,
we will elucidate the LPS footprint on the CVB3 virion. Finally, in Aim 3, we will determine the effect of
lipopolysaccharide on CVB3 infectivity and viral stability. Overall, this project will significantly impact our
understanding of viral-microflora interactions and aid future studies to identify antiviral targets for the
development of novel therapeutics.

## Key facts

- **NIH application ID:** 10520111
- **Project number:** 1R01AI165611-01A1
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Christopher Michael Robinson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $476,554
- **Award type:** 1
- **Project period:** 2022-07-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10520111

## Citation

> US National Institutes of Health, RePORTER application 10520111, Bacterial-mediated enhancement of Coxsackievirus (1R01AI165611-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10520111. Licensed CC0.

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