# The Role of IFI35 in Innate Immunity and Influenza Pathogenesis

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2020 · $381,250

## Abstract

PROJECT SUMMARY
Influenza virus is an important human pathogen that can cause severe disease and death in humans. Highly
pathogenic influenza viruses, such as H5N1, induce excessive host responses associated with pro-
inflammatory cytokine production, recruitment of innate immune cells and a diminished adaptive immune
response. The host proteins involved in this pathogenic response are largely unknown. This information is
important and will provide a framework for the rational design of new treatments against pathogenic influenza
infection.
We have previously identified interferon induced protein 35 (IFI35) as a host gene associated with
susceptibility to highly pathogenic H5N1 influenza A virus (2, 3). We now present data showing a direct link
between murine IFI35 and exacerbation of influenza-virus induced disease. IFI35 knockout mice infected with
the highly pathogenic H5N1 influenza virus recovered more rapidly compared to congenic wild type mice,
producing less pro-inflammatory cytokines, such as IL12p40, G-CSF and KC. Correspondingly, bone marrow
macrophages derived from IFI35 knockout mice produced significantly less IL12p40 following stimulation with a
TLR3 agonist. The IL12p40 is produced as a homodimer (IL12p402) which is a chemo attractant and pre-
inflammatory cytokine. In summary, IFI35 appears to be a key regulator of the inflammatory response following
viral infection. This proposal is aimed at characterizing how IFI35 protein modulates IL12p40 and IL12p402
production after influenza virus infection and investigating mechanistically how IFI35 shapes the inflammatory
environment and disease outcome.

## Key facts

- **NIH application ID:** 9913449
- **Project number:** 5R01AI118938-05
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Adrianus CM Boon
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $381,250
- **Award type:** 5
- **Project period:** 2016-05-10 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9913449

## Citation

> US National Institutes of Health, RePORTER application 9913449, The Role of IFI35 in Innate Immunity and Influenza Pathogenesis (5R01AI118938-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9913449. Licensed CC0.

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