OPUS grant to investigate mechanisms of viral immune evasion

01 07 2026

Prof. Agnieszka Kwiatek from the Department of Molecular Virology, Institute of Microbiology, has received PLN 1,993,900 in funding from the National Science Centre under the OPUS 30 call for the project entitled “Mitochondrial remodeling by respiratory viral non-structural proteins as a mechanism of macrophage immunoreprogramming”.

Respiratory viruses, such as RSV, influenza A virus, and SARS-CoV-2, pose a significant challenge to public health, causing diseases ranging from mild respiratory infections to severe, life-threatening conditions. Despite advances in virology and immunology, many aspects of virus–host interactions remain poorly understood, particularly the mechanisms that allow viruses to evade immune responses and persist in tissues. Understanding these processes is crucial for developing effective antiviral therapies and for preventing the long-term consequences of viral infections. Interactions between epithelial cells, which are the primary site of infection, and immune cells such as macrophages play a critical role in shaping early immune responses and the course of infection.

The aim of this project is to investigate the mechanisms by which viral non-structural proteins disrupt mitochondrial ultrastructure in epithelial cells and to examine how these changes affect macrophage function. The researchers hypothesize that changes in mitochondrial structure trigger epithelial cells to release paracrine factors that modulate macrophage activity, promoting a shift in their phenotype from pro-inflammatory to immunoregulatory. This macrophage state may weaken antiviral responses and promote viral persistence in tissues. Studying these mechanisms is particularly important given the substantial impact of respiratory viruses on public health and the limited knowledge regarding their ability to manipulate cellular metabolism and immune signalling.

The project will investigate the effects of viral non-structural proteins on mitochondria and include functional analyses of their impact on communication between epithelial cells and macrophages. A key aspect of the project is the use of advanced organ-on-a-chip microfluidic technology, which allows the reconstruction of complex epithelial microarchitecture and dynamic cell–cell interactions under conditions that mimic human tissues. This approach enables precise modelling of epithelial–macrophage communication under medium flow and controlled gradients of paracrine factors, increasing the biological relevance of the results and allowing better prediction of in vivo responses. Additionally, molecular and transcriptomic analyses will be employed to determine changes in gene expression and signalling pathways in macrophages, along with ultrastructural imaging of mitochondria to assess the impact of viral non-structural proteins on mitochondrial organization and function. An essential aspect of the project is the identification of paracrine factors, secreted by epithelial cells expressing viral non-structural proteins, which are critical for modulating macrophage responses.

The results will provide a better understanding of respiratory viruses’ strategies to evade immune responses and may open new avenues for treatment and prevention of viral infections.

Warm congratulations on receiving the grant, and best wishes for the successful completion of the project!

Details of the National Science Centre funding calls are available at:
https://www.ncn.gov.pl/aktualnosci/2026-06-11-wyniki-opus30-sonata21