# REGULATION OF HOST RESPONSES TO RESPIRATORY VIRAL INFECTION BY ISG15

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2021 · $393,750

## Abstract

The host response to viral infection is complex and must balance inhibiting replication of the pathogen (disease
resistance) with limiting damage to the host (disease tolerance). A key mediator of the host response to viral
infection are type I interferons and the hundreds of interferon stimulated genes they induce. Among these, the
ubiquitin-like protein ISG15, functions as an antiviral protein, limiting replication of many viruses. Our studies
have demonstrated that ISG15 can also regulate the host response and recovery from viral infection,
independent of any effects on viral replication, a process known as disease tolerance. During respiratory viral
infection we have detected increased epithelial damage in both cells and mice lacking ISG15. In this proposal
we will explore the mechanism by which ISG15 protects the epithelium from damage during acute viral
infection. In Aim 1 we will determine if ISG15 protects the host by regulating the type of cell death, apoptosis
vs. necroptosis, initiated in respiratory epithelial cells during acute viral infection. In Aim 2 we will determine if
ISG15, through its interactions with RIPK1 and RIPK3, functions as a molecular switch to regulate the
induction of necroptosis and apoptosis during influenza A virus infection. Understanding the mechanism by
which ISG15 protects the host from viral infection, both through inhibition of viral replication and by limiting the
damage induced to the host may lead to the development of therapies that target this pathway and can be
used for the treatment of acute viral infections.

## Key facts

- **NIH application ID:** 10169225
- **Project number:** 5R01AI080672-08
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Deborah J Lenschow
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $393,750
- **Award type:** 5
- **Project period:** 2009-08-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10169225

## Citation

> US National Institutes of Health, RePORTER application 10169225, REGULATION OF HOST RESPONSES TO RESPIRATORY VIRAL INFECTION BY ISG15 (5R01AI080672-08). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10169225. Licensed CC0.

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