# Transcriptional and non-transcriptional functions of IRF3 in ALD

> **NIH NIH R01** · CLEVELAND CLINIC LERNER COM-CWRU · 2020 · $160,944

## Abstract

ABSTRACT
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-
CoV-2) is a highly contagious and fast-spreading infectious disease, which reached pandemic status in only four
months and is spreading worldwide with millions of people being affected. The clinical spectrum of COVID-19
ranges from mild to critically ill diseases. COVID-19 can progress rapidly into acute respiratory distress syndrome
(ARDS), multiorgan failure, and even death. In the midst of the COVID-19 epidemic, there is some evidence for
increased alcohol purchases. Since people generally buy more alcohol during epidemics, increased alcohol
consumption may result in reduced resistance to infections like COVID-19 and promote the progression of the
disease. SARS-COV-2 is a positive-sense single stranded RNA (ssRNA). While alcohol consumption has not
yet been shown to directly increase risk for SARS-COV-2 transmission or COVID-19 severity, alcohol negatively
affects the both the innate and adaptive immune systems and increases risk for many infectious diseases.
Importantly, recent data from both murine models of ethanol exposure and peripheral blood mononuclear cells
(PBMCs) from patients with alcohol-associated hepatitis (AH) indicate that signaling by viral ss/dsRNA is
disrupted by alcohol, analogous to impact of alcohol on signaling via bacterial products, such as LPS. The parent
RO-1 (Transcriptional and non-transcriptional roles of IRF3 in ALD) for this URGENT COMPETITIVE RENEWAL,
we are investigating the impact of chronic ethanol on ss/ds RNA sensing and activation of IRF3-mediated cellular
responses. Here we propose to extend the scope of this RO1 to address two important aspects of the interaction
of alcohol and COVID-19 in people consuming alcohol. In Specific Aim 1, making use of data from the UK
Biobank, we will ask whether alcohol consumption or alcohol-related diseases increase risk of infection,
hospitalization and mortality. In Specific Aim 2, we will use single cell RNA seq analysis to interrogate the impact
of alcohol consumption on anti-viral responses in peripheral innate and adaptive immune cells. Understanding
the impact of alcohol use on risk for COVID-19 and characterizing the specific cellular changes in anti-viral
responses will meet an important unmet clinical need for guiding public health and medical responses to the
COVID-19 pandemic.

## Key facts

- **NIH application ID:** 10173028
- **Project number:** 3R01AA027456-02S1
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** LAURA E. NAGY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $160,944
- **Award type:** 3
- **Project period:** 2019-07-05 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10173028

## Citation

> US National Institutes of Health, RePORTER application 10173028, Transcriptional and non-transcriptional functions of IRF3 in ALD (3R01AA027456-02S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10173028. Licensed CC0.

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