Résilience - COVID-19 - Résilience - Coronavirus disease 2019

SARS-CoV-2 dissemination from a macrophage point of view – Macro-SARS

Submission summary

SARS-CoV-2, the etiological agent of COVID-19, infects lung epithelial cells and resident alveolar macrophages leading to lung injuries in patients with severe COVID-19, and triggering macrophage activation syndrome or "cytokine storm". Macrophages can be found in lungs as large multinucleated cells, also called syncytia, and their presence might result in damages in pulmonary tissues. In addition, dissemination of virus-containing macrophages migrating out of the lungs to other tissues may contribute to viral spread and failure of multiple organs. Macrophages can be directly infected through the main receptor of SARS-CoV-2, ACE2 (Angiotensin-converting enzyme 2). However, in contrast to lung epithelial cells, macrophages are poorly susceptible to cell-free infection and our hypothesis is that they could be more prone to be infected by cell-to-cell viral transfer through the formation of multinucleated giant cells (MGCs). In addition, the formation of tunneling nanotubes (TNT), that are F-actin-containing intercellular bridges essential for macrophage cell-to-fusion, may promote cell-cell fusion for intercellular spreading of SARS-CoV-2. Thus, this project will first compare infection of monocyte-derived macrophages with cell-free SARS-CoV-2 or by virus cell-to-cell transfer from infected epithelial cells. We will also characterize the cellular mechanisms involved in macrophage infection by virus cell-to-cell transfer, with a special focus on TNT and MGC formation, and study the impact of SARS-CoV-2 infection on macrophage migration in 3D. This project will give access to crucial information for SARS-CoV-2 pathogenesis, including virus spreading between the different target cells and dissemination in tissues.

Project coordination

Christel Vérollet (INSTITUT de PHARMACOLOGIE et de BIOLOGIE STRUCTURALE)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

IPBS INSTITUT de PHARMACOLOGIE et de BIOLOGIE STRUCTURALE

Help of the ANR 80,000 euros
Beginning and duration of the scientific project: April 2021 - 12 Months

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