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LASSA VIRUS RECEPTOR

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The interaction of Lassa virus with its cellular receptor alpha dystroglycan

The arenavirus Lassa fever virus (LFV) causes a severe viral hemorrhagic fever in humans with over 300, 000 infections and thousands of deaths annually. Fatal LFV infection is characterized by marked immunosuppression of the patie... ver más

29/02/2012

CHUV

100K€

Presupuesto del proyecto: 100K€

Líder del proyecto

CENTRE HOSPITALIER UNIVERSITAIRE VAUDOIS No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo FP7 notifico la concesión del proyecto el día 2012-02-29 No tenemos la información de la convocatoria

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1 Participantes

CHUV

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Líder del proyecto

CENTRE HOSPITALIER UNIVERSITAIRE VAUDOIS No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 100K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto The arenavirus Lassa fever virus (LFV) causes a severe viral hemorrhagic fever in humans with over 300, 000 infections and thousands of deaths annually. Fatal LFV infection is characterized by marked immunosuppression of the patient, resulting in uncontrolled viral infection with progressive hemorrhagic disease and shock. Since death occurs in absence of a significant anti-viral immune response, the fatal disease is caused by virus-induced changes in host cell function, rather than immunopathology. The analysis of the virus-host cell interaction is therefore of great importance to understand this disease and to develop novel therapeutic strategies. Binding of a virus to its cellular receptor(s) is not only the first step of virus infection but represents also a promising target for therapeutic intervention. The cellular receptor of LFV is alpha-dystroglycan (alpha-DG), an important cell surface receptor for proteins of the extracellular matrix (ECM). Based on the pivotal importance of alpha-DG for normal host cell biology, the interaction of LFV with its receptor is of particular interest regarding virus-cell interaction and viral pathogenesis. Using a combination of biochemical and cell biological techniques we will investigate the role of the virus-receptor interaction for infection and viral pathogenesis. Since alpha-DG is involved in cellular signal transduction, we will investigate the impact of virus binding on receptor-mediated signaling in the host cell. In a next step, we will address the role of virus-induced receptor signaling for virus infection and its consequences for the host cell. Our recent studies showed that expression of the envelope glycoprotein (GP) of LFV in cells results in down-regulation of functional alpha-DG. In the present project, we will investigate the impact of this virus-receptor interference on the function of vascular endothelial cells, which play a key role in the pathogenesis of Lassa hemorrhagic fever.

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