# Uncovering and harnessing connected metabolic pathways essential to virus infection.

> **NIH NIH R35** · LOYOLA UNIVERSITY CHICAGO · 2020 · $368,430

## Abstract

Project Summary / Abstract
Polyamines are small molecules abundant in eukaryotic cells that function in transcription and translation.
While these molecules are important for cellular function, emerging evidence suggests that polyamine
metabolism is intricately linked to diverse metabolic pathways within the cell. The interconnectedness of
metabolic pathways has significant consequences for cells, as well as pathogens. We previously demonstrated
that polyamines support replication of diverse RNA viruses and that upon detection of infection, cells induce
polyamine depletion. Polyamine depletion limits infection by bunyaviruses (Rift Valley fever virus [RVFV] and
La Crosse virus [LACV]), flaviviruses (Zika virus [ZIKV] and dengue viruses), and enteroviruses
(Coxsackievirus B3 [CVB3], rhinovirus), among several others. We hypothesize that these distinct virus
families subvert cellular metabolism, specifically through polyamines, to support virus replication.
Here, we will investigate (1) how viruses utilize polyamines at distinct stages of replication, (2) how viruses
confront polyamine depletion, and (3) how polyamine biosynthesis connects to other metabolic pathways to
support virus replication.
We use the RVFV, ZIKV, and CVB3 model systems in our work because these viruses represent three
evolutionarily distant viruses with different replicative and structural differences. While each of these viruses
relies on polyamines for replication, we find that how they use polyamines is different. Now, we will expand on
this work to understand the roles of distinct polyamines during virus infection, including roles in virion structure,
cellular attachment, and genome replication. We will also use these model systems to understand how these
viruses manipulate polyamine metabolism. Finally, we will investigate how the differences in polyamine
utilization may reflect how polyamines affect other cellular metabolic pathways, including lipid and cholesterol
synthesis. This work will illuminate the connectedness of polyamine biosynthesis to other metabolic pathways
and how viruses rely on these interconnected pathways for successful replication. This work will highlight
fundamental roles for polyamines in virus replication and in cellular metabolism.

## Key facts

- **NIH application ID:** 10029347
- **Project number:** 1R35GM138199-01
- **Recipient organization:** LOYOLA UNIVERSITY CHICAGO
- **Principal Investigator:** Bryan C Mounce
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $368,430
- **Award type:** 1
- **Project period:** 2020-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10029347

## Citation

> US National Institutes of Health, RePORTER application 10029347, Uncovering and harnessing connected metabolic pathways essential to virus infection. (1R35GM138199-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10029347. Licensed CC0.

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