# Dissecting ADP-ribosylation as an innate immune response countering influenza virus replication

> **NIH NIH R21** · UNIVERSITY OF WISCONSIN-MADISON · 2022 · $195,030

## Abstract

ABSTRACT
Viral infections manipulate diverse post-translational modifications (PTMs), altering existing protein landscapes
to create cellular environments favorable to replication. PTMs allow for rapid modulation of host environments
by altering protein abundance, localization, and activity. Because of their dynamic nature, PTMs typify ideal
immune response effectors or initiators. Our data identifies ADP-ribosylation, the modification of proteins with
ADP-ribose (ADPr), as a rapid, immune-like response from infected cells that constitutes an antiviral response
that counters influenza virus infection. Using cutting-edge ADPr-specific mass spectrometry approaches, we
have characterized with single amino acid resolution the ADP-ribosylome during influenza virus infection and
identified thousands of modifications on viral and host proteins. ADP-ribosylation has been associated with
antiviral responses against multiple viruses. However, little is known about how viral infections trigger this
response or the activiral mechanism(s) of ADP-ribosylation and poly(ADPr)-polymerases (PARPs), the enzymes
that catalyze addition of ADPr to proteins. Here, we propose studies of ADP-ribosylation during influenza virus
infection. We will identify the functional consequences of specific ADPr modifications, and building on our unique
ADP-ribosylome dataset, investigate how ADP-ribosylation alters the function of specific viral and host proteins.
We will interrogate the cellular pathways responsible for initiating ADP-ribosylation responses, defining the
molecular triggers and PARPs that are activated during influenza virus infection. These experiments will
elucidate the mechanisms of ADPr-mediated viral inhibition, the factors that trigger this response, and how
viruses counter it, establishing ADP-ribosylation as a key aspect of cellular antiviral responses and perhaps as
an entirely independent arm of antiviral defenses.

## Key facts

- **NIH application ID:** 10493284
- **Project number:** 5R21AI160779-02
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Andrew Mehle
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $195,030
- **Award type:** 5
- **Project period:** 2021-09-22 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10493284

## Citation

> US National Institutes of Health, RePORTER application 10493284, Dissecting ADP-ribosylation as an innate immune response countering influenza virus replication (5R21AI160779-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10493284. Licensed CC0.

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