# Interplay between influenza virus and S1P-metabolizing enzymes

> **NIH NIH R01** · UNIVERSITY OF MISSOURI-COLUMBIA · 2022 · $449,648

## Abstract

Project Summary
Influenza, as a global threat to human health, continues to cause significant morbidity and high rates of
mortality. To effectively control influenza, it is important to understand the interplay between the host and
influenza by identifying host factors that regulate viral replication and defining the mechanisms by which
influenza virus manipulates the cellular defense or signaling pathway. Sphingolipids are bioactive lipid
mediators and include sphingosine 1-phosphate (S1P). Although S1P and its metabolizing enzymes, such as
S1P lyase (SPL) and sphingosine kinase 2 (SK2), have been reported to regulate versatile cellular or disease
processes, their roles in influenza virus infection are poorly understood. Preliminary data indicate that SPL
promoted IKKε-mediated type I interferon (IFN) responses to display anti-influenza viral activity. However,
influenza viruses effectively downregulated SPL, suggesting that influenza virus strives to evade the host
defense mechanism. Furthermore, influenza virus increased the level of another S1P-metabolizing enzyme,
SK2, which accelerated influenza virus replication. Inhibition of SK2 impaired influenza virus propagation in
vitro and increased the viability of virus-infected mice, demonstrating the pro-influenza function of SK2. These
findings heighten the need to further investigate the interplay between the S1P-metabolizing enzymes, host
defense and signaling, and influenza virus. The research aims of this proposal include 1) determining the
mechanisms by which influenza virus manipulates SPL and SK2 to enhance virus replication, 2) investigating
the mechanisms of how these S1P-metabolizing enzymes display antiviral or pro-influenza viral activities, and
3) establishing the functions of the S1P-metabolizing enzymes during influenza virus infection in vivo.
Collectively, these research results can define the regulatory functions of S1P-metabolizing enzymes that
impact host defenses and influenza pathogenicity. Furthermore, the project could provide a foundation for
designing new therapeutic interventions to cure influenza.

## Key facts

- **NIH application ID:** 10426374
- **Project number:** 5R01AI162631-02
- **Recipient organization:** UNIVERSITY OF MISSOURI-COLUMBIA
- **Principal Investigator:** BUMSUK HAHM
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $449,648
- **Award type:** 5
- **Project period:** 2021-06-10 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10426374

## Citation

> US National Institutes of Health, RePORTER application 10426374, Interplay between influenza virus and S1P-metabolizing enzymes (5R01AI162631-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10426374. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*