Molecular pathology of anti-viral T cell responses in the central nervous system

Projektinformationen

PATHOCODE

ID Finanzhilfevereinbarung: 865026

DOI

10.3030/865026

Projekt abgeschlossen

EK-Unterschriftsdatum 16 März 2020

Startdatum 1 August 2020

Enddatum 31 Januar 2026

Finanziert unter

• EXCELLENT SCIENCE - European Research Council (ERC)

Gesamtkosten

€ 1 999 954,00

EU-Beitrag

€ 1 999 954,00

Koordiniert durch

UNIVERSITE DE GENEVE
Switzerland

Periodic Reporting for period 3 - PATHOCODE (Molecular pathology of anti-viral T cell responses in the central nervous system)

Berichtszeitraum: 2023-08-01 bis 2025-01-31

Zusammenfassung vom Kontext und den Gesamtzielen des Projekts

Inflammatory diseases affecting the central nervous system (CNS) can lead to severe long-term health consequences, including difficulty with movement, speech, memory, or thinking with a significant impact on individuals and their families. In such conditions, the immune system may attack non-renewable neurons, which are cells that are vital for transmitting signals in the CNS. Even in cases in which the virus has been eliminated from the CNS by the immune system, neuronal functional impairments can persist, but the molecular basis of such alterations are not yet well understood.

The PATHOCODE research project aims to identify disease-relevant alterations of signaling pathways that are activated when the immune system attacks neurons, and how this results in functional changes in the short and long term. The overall objective is to understand the molecular processes that underlie such functional impairments, which could be targeted by future therapies to improve outcomes for patients. By unraveling the molecular mechanisms underlying immune attacks on neurons, this research could lead to better treatments for inflammatory diseases affecting the CNS, such as viral infections.

Arbeit, die ab Beginn des Projekts bis zum Ende des durch den Bericht erfassten Berichtszeitraums geleistet wurde, und die wichtigsten bis dahin erzielten Ergebnisse

In this research project, we are investigating how the immune system interacts with neurons in the central nervous system (CNS) during a viral infection. We are using an animal model of virus encephalitis to study the changes that occur in neurons during different stages of the disease. By analyzing the genetic information in the neurons, we have been able to identify specific changes in gene expression that occur as a result of the viral infection and subsequent immune cell attack.
We are also investigating structural and functional neuronal changes, and how these are related to alterations of neuronal connections. By comparing infected and non-infected neurons, we have been able to identify which molecular changes are directly related to the virus infection of a cell and which are a result of the inflamed tissue microenvironment. We are also investigating how immune cell engagement can alter the metabolism of neurons during CNS inflammation.
Our research will help to understand how immune-mediated virus clearance can be associated with long-lasting alterations and provides novel molecular targets that may be used to reverse such alterations. By understanding the molecular underpinnings of immune cell engagement with neurons, we hope to provide a basis for new treatments in viral encephalitis and other neuroinflammatory diseases.

Fortschritte, die über den aktuellen Stand der Technik hinausgehen und voraussichtliche potenzielle Auswirkungen (einschließlich der bis dato erzielten sozioökonomischen Auswirkungen und weiter gefassten gesellschaftlichen Auswirkungen des Projekts)

Our project will shape our fundamental understanding of how chronic inflammatory processes can sustainably affect neuronal function in the CNS with potential implications for human viral infection but also for chronic autoimmune disease conditions. Deciphering the downstream molecular pathways triggered by an immune cell attack on neurons and its causality to their proper function is key to understanding how distinct alterations in neurons can emerge in chronic inflammatory CNS diseases. Gaining insights into this poorly explored relationship will also provide the basis for the development of novel therapeutic approaches in the context of CNS virus infection and human autoimmune diseases that aims to protect or even revert neurological decline in patients suffering from such chronic diseases.