# Prenylation in antiviral immunity

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2024 · $632,371

## Abstract

Summary
In this proposal, we will explore the role of prenylation in antiviral immunity. Prenylation is a post-translational
modification that renders proteins hydrophobic, thus targeting them to the endomembrane. While the role of
prenylation in immunity is unclear, our preliminary data shows compelling evidence that prenylation is a
modification widely used in innate antiviral immunity. As both the host and virus utilize prenylation and the
cholesterol biosynthetic pathway, we propose a dynamic host-pathogen interaction at this interface. We
hypothesize that prenylation could be a potent host innovation to counter viral pathogenesis. This is based on
in silica analysis that revealed an enrichment of immunity-related proteins with a prenylation motif. We
followed in-silica analyses with a biochemical screen and identified several prenylated antiviral proteins that
are involved in interferon responses and virus restriction, with potential to affect virus entry, replication, and
egress. In this grant, we propose to identify the functional consequences of prenylated proteins on subcellular
localization, interferon signaling, and antiviral function. By perturbing specific enzymes in the prenylation
pathway, we will study its effect on interferon response, antiviral effectors, and virus control. This work will
provide novel insights into cell-intrinsic antiviral countermeasures and the development of novel antiviral drug
targets.

## Key facts

- **NIH application ID:** 10786144
- **Project number:** 5R01AI175724-02
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Ram Savan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $632,371
- **Award type:** 5
- **Project period:** 2023-02-14 → 2028-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10786144

## Citation

> US National Institutes of Health, RePORTER application 10786144, Prenylation in antiviral immunity (5R01AI175724-02). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10786144. Licensed CC0.

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