# Lung MIWI2 and the host defense against Influenza A virus

> **NIH NIH F31** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2022 · $46,752

## Abstract

Abstract
Influenza is one of the most common respiratory infections globally and has led to an alarming number of deaths
annually. Seasonal vaccines and therapies vary in efficacy among higher risk patients although they currently
serve as the only countermeasures. This presents a critical need to further understand the host response to
influenza in order to uncover pathways that can be targeted using novel therapies. One of the target cells of
Influenza A virus (IAV) are the multiciliated cells of the lung airway. Our lab had previously discovered a subset
of multiciliated cells defined by the expression of MIWI2, an Argonaute family protein most commonly studied in
mammalian testes. MIWI2 binds to PIWI-interacting RNA (piRNA) and suppresses retrotransposon activity in
germline cells to maintain genome integrity. However, MIWI2 expression in somatic cells is not well understood.
In order to understand lung MIWI2, we used a MIWI2-TdTomato heterozygote (haplo-sufficient) and a
homozygote (deficient) knock-in reporter mouse model. Mice deficient in MIWI2 exhibited a markedly decrease
burden of Influenza A virus suggesting that MIWI2 plays a critical role in regulating viral pathogenesis and the
immune response. Incorporating an HA-mNeon reporter IAV, we ruled out the possibility that MIWI2 multiciliated
cells were preferentially infected as we observed no differences in viral tropism between MIWI2 haplo-sufficient
and deficient mice. Recently, we identified the presence of an immune cell population that also expresses
MIWI2, raising the prospect that this heretofore unrecognized hematopoietic cell could be key to MIWI2
dependent immune function. Taken together, we hypothesize that a MIWI2 expressing cell in the lung critically
modulates the host response to IAV infection. We will examine our central hypothesis by pursuing two aims. In
the first Aim, we will use bone marrow transplantations and cell-specific deletion of MIWI2 mouse models to
determine the identity of the MIWI2 expressing cell population that modulates the immune response during an
IAV infection. In the second Aim, we will employ single cell sequencing to elucidate MIWI2-dependent pathways
that critically regulate the lung’s antiviral immune response. Overall, the work proposed here will expand our
understanding of the viral pathogenesis of IAV as well as uncover novel pathways that are involved in the lung’s
host immune response. These studies will also provide functional information regarding the action of Argonaute
proteins in somatic cells. Most importantly, this serves as a platform for an integrated and cogent training plan
that will support my development as an independent researcher.

## Key facts

- **NIH application ID:** 10537855
- **Project number:** 1F31HL165892-01
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Jhonatan Henao Vasquez
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $46,752
- **Award type:** 1
- **Project period:** 2022-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10537855

## Citation

> US National Institutes of Health, RePORTER application 10537855, Lung MIWI2 and the host defense against Influenza A virus (1F31HL165892-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10537855. Licensed CC0.

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