# The role of macrophage podosomes in Ebola virus pathogenesis

> **NIH NIH R21** · TEXAS BIOMEDICAL RESEARCH INSTITUTE · 2021 · $297,000

## Abstract

PROJECT SUMMARY
Ebola virus (EBOV) is an emerging, highly pathogenic virus associated with increasingly more frequent
outbreaks of hemorrhagic disease in human populations. Approved countermeasures to prevent or treat EBOV
disease are currently limited. Macrophages are the initial cells targeted by EBOV, and yet, little is known about
the exact nature of EBOV-macrophage surface interactions and subsequent uptake into the cell. Due to their
migratory properties, macrophages are also believed to rapidly disseminate the virus to distant tissues and
organs despite the lack of experimental evidence. We have preliminary data showing that EBOV depends on
podosomes, mechanosensitive adhesive structures used by macrophages to migrate through tissues and
sample antigens, to enter macrophages. The data also shows that EBOV replication increases macrophage
locomotion through a fibrillar 3D matrix and reduces podosome number, suggesting that the virus actively
transforms infiltration of tissues by these cells. This proposal aims to examine the interactions between EBOV
and podosomes. In Aim 1, we will determine whether podosomes serve as ports for EBOV entry into human
macrophages. In Aim 2, we will characterize migratory and invasive properties of macrophages challenged with
EBOV. In Aim 3, we will assess host resistance to systemic infection with EBOV in a mouse model of EBOV
disease devoid of functional macrophages. Our findings will establish a new model of interactions between EBOV
and macrophages, laying the groundwork for further investigations into pathogenesis of filoviruses. Importantly,
these discoveries may lead to new areas of development of novel countermeasures targeting EBOV and related
viruses.

## Key facts

- **NIH application ID:** 10129147
- **Project number:** 1R21AI151717-01A1
- **Recipient organization:** TEXAS BIOMEDICAL RESEARCH INSTITUTE
- **Principal Investigator:** Olena Shtanko
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $297,000
- **Award type:** 1
- **Project period:** 2020-11-12 → 2022-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10129147

## Citation

> US National Institutes of Health, RePORTER application 10129147, The role of macrophage podosomes in Ebola virus pathogenesis (1R21AI151717-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10129147. Licensed CC0.

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