# Regulation of the interferon lamda receptor by influenza

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2022 · $556,562

## Abstract

Influenza is a leading cause of death in the US with a staggering economic burden. Interferons
serve as a critical response to this virus triggering elaboration of host defense molecules within
alveolar macrophages. A relatively new and unchartered area in interferon biology involves
interferon lamda (IFN) acting through its cognate receptor, IFNLR1, to mediate anti-viral
defense. Loss of IFNLR1 leads to viral dissemination and death in experimental influenza. The
mechanistic platform of this proposal resides on our discovery of a unique molecular model
whereby a protein, Fbxo45, rapidly impairs host defense by mediating ubiquitin-driven disposal
of this crucial cytoprotective, anti-viral receptor, IFNLR1. Hence, in this application we will first
elucidate how short-term influenza infection depletes IFNLR1 through Fbxo45, thereby
accentuating experimental viral lung injury (Aim 1). We will specifically elucidate how Fbxo45
targets IFNLR1 for its degradation using complementary in vitro and in vivo genetic models.
Next, after sustained influenza infection we observed that IFNLR1 mRNA levels increase in
macrophages, perhaps as a compensatory host defense mechanism. Here we will assess
novel post-transcriptional mechanisms mediated by microRNA acting on the 3’UTR of the
IFNLR1 gene (Aim 2). These studies will provide a new pathobiologic model of lung injury that
will serve as a platform for unveiling new molecular insight into the IFN- IFNLR1 axis that is
indispensable to resolve inflammatory injury in subjects with severe virally-driven critical illness.

## Key facts

- **NIH application ID:** 10456935
- **Project number:** 5R01HL081784-13
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Rama K Mallampalli
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $556,562
- **Award type:** 5
- **Project period:** 2006-04-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10456935

## Citation

> US National Institutes of Health, RePORTER application 10456935, Regulation of the interferon lamda receptor by influenza (5R01HL081784-13). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10456935. Licensed CC0.

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