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Biological relevance of the multiple infection unit as a novel target for antivi...

Biological relevance of the multiple infection unit as a novel target for antiviral development The last decade of research in enteric virus infection produced a body of compelling evidences that challenged the paradigm of the single infection unit, where a single virus is able to elicit infection of a target cell. Instead,... ver más

31/10/2022

UZL

226K€

Presupuesto del proyecto: 226K€

Líder del proyecto

UNIVERSITAET zu LUEBECK No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

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Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2022-10-31

MSCA-IF-2018: Individual Fellowships Objective:The goal of the Individual Fellowships is to enhance the creative and innovative potential...

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3 Participantes

UZL

226.01K€ | Lider

UNIVERSITY OF MICHIGAN THE R...

144.61K€ | Participante

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Duración del proyecto: 43 meses Fecha Inicio: 2019-03-27
Fecha Fin: 2022-10-31

Líder del proyecto

UNIVERSITAET zu LUEBECK No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 226K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto The last decade of research in enteric virus infection produced a body of compelling evidences that challenged the paradigm of the single infection unit, where a single virus is able to elicit infection of a target cell. Instead, observational studies of infection in vivo and in vitro suggest that enteric viruses travel in groups: in vesicles with inverted phosphatidylserine topology or at the surface of commensal bacteria. It has been proposed that both strategies increase locally the viral multiplicity of infection, thus favoring viral complementation of defective genomes. There is a lack of knowledge on the biological relevance of the so-called multiple infection unit (MIU) as it has not been mechanistically studied in physiologically relevant model of the GI tract. In addition, the MIU is a strategy employed by all the enteric viruses so far tested, therefore it might represent a valuable target for the design of broad spectrum therapeutics. The central hypothesis of this project is that targeting MIU will inhibit enteric virus infection ex vivo and in vivo. My model of enteric virus is human norovirus (HNoV) for its clinical relevance and for its well described interaction with commensal bacteria. In work package (WP)1, to gain insight on the biological relevance of MIU in ex vivo physiologically relevant models, I will test the hypothesis that MIU increases HNoV infection in human intestinal enteroids. In aim 2, I will develop an in vitro screening platform by pulldown assay with His-tagged HNoV virus-like particles to i) screen for small molecules inhibitors of the infection and ii) identify bacterial species that are bound to HNoV in stool derived from healthy volunteer and diseased patients (i.e. inflammatory bowel disease, Crohn) . In aim 3, in order to provide evidence that targeting MIU blocks viral infection, I will test the efficacy of the small molecules identified in aim 2 in the ex-vivo model established in aim 1 and/or in-vivo, in a murine model.

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