# Dual oxidase and lactoperoxidase in influenza infection

> **NIH NIH R01** · UNIVERSITY OF GEORGIA · 2023 · $377,500

## Abstract

Project summary description
 Influenza virus infections affect millions of people worldwide every year and cause serious mortality.
Current treatment options are limited to viral strain-specific vaccination and are problematic due to antiviral drug
resistance. There is an urgent need to identify novel host innate immune mechanisms providing broad range
protection against influenza. Bronchial epithelial cells orchestrate an oxidative extracellular antimicrobial system
present in the airway surface liquid consisting of the protein lactoperoxidase (LPO), the thiocyanate anion (SCN-
) and hydrogen peroxide (H2O2). LPO oxidizes SCN- using H2O2 into hypothiocyanite (OSCN-) that has known in
vitro antiviral effects. Dual oxidase 1 (Duox1), an NADPH oxidase highly expressed in bronchial epithelial cells,
is the H2O2 source for the system. Our long-term goal is to determine whether the Duox1/H2O2/LPO/SCN-
antiviral system could be manipulated in influenza infection for therapeutic purposes in human patients. The
objective of this proposal is to determine and characterize the antiviral role of Duox1 and LPO against influenza
in multiple experimental systems. Our preliminary data show that 1) primary bronchial epithelial cells inactivate
several influenza viruses in an Duox1/H2O2/LPO/SCN- -dependent manner, 2) Duox1-deficient mice have
increased mortality and morbidity, impaired viral clearance and leukocyte recruitment following influenza
infection in vivo, and 3) the in vitro influenza-inactivating effect of this mechanism can be enhanced to inhibit
influenza infection. Based on these data, our central hypothesis is that the Duox1/H2O2/LPO/SCN- system
attenuates influenza infection, both in vitro and in vivo, and can be boosted to fight influenza. The rationale for
the proposed research is that there is a need to better understand how powerful the antiviral Duox1/LPO-based
system is and how can it be manipulated for therapeutic purposes. The main hypothesis will be tested in cell-
free, airway epithelial and mouse model systems using a wide range of influenza strains. It is anticipated that
our aims will yield several impactful outcomes including 1) detailed description of the anti-influenza mechanism
of action of the Duox1/H2O2/LPO/SCN- system; 2) determination of the in vivo relevance of Duox1 in fighting a
wide range of influenza strains; and 3) exploring the therapeutic potential of the Duox1/H2O2/LPO/SCN- system
to improve influenza clearance and to diminish associated lung damage. Our innovative work shows that the
Duox1/H2O2/LPO/SCN- system inactivates influenza, and uses a Duox1-deficient mouse strain for in vivo studies.
The significance of the outlined work relies in establishing the relevance of a novel innate immune mechanism
of the airways that can be enhanced to attenuate influenza infections or applied in conjunction with influenza
vaccines to potentially enhance efficacy. In summary, our proposed work will have a positive impact in the fie...

## Key facts

- **NIH application ID:** 10556348
- **Project number:** 5R01AI146857-04
- **Recipient organization:** UNIVERSITY OF GEORGIA
- **Principal Investigator:** Balazs Rada
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $377,500
- **Award type:** 5
- **Project period:** 2020-02-19 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10556348

## Citation

> US National Institutes of Health, RePORTER application 10556348, Dual oxidase and lactoperoxidase in influenza infection (5R01AI146857-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10556348. Licensed CC0.

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