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Elucidating the molecular mechanism by which BTN3A3 mediates host restriction against zoonotic influenza virus infection.

Descrizione del progetto

Approfondimenti sulla trasmissione zoonotica dell’influenza aviaria

La zoonosi è una malattia infettiva causata da un agente patogeno che si è diffuso da un animale a un essere umano. Uno di questi agenti patogeni zoonotici che pongono un serio rischio per la salute globale è il virus dell’influenza aviaria, una particella in grado di replicarsi nel nuovo organismo ospitante superando le sue barriere specifiche, come la proteina BTN3A3, che impedisce a tale virus di replicarsi nelle cellule umane. Con il sostegno del programma di azioni Marie Skłodowska-Curie, il progetto FluZoBa studierà le modalità con cui le mutazioni virali aiutano il virus dell’influenza aviaria a eludere BTN3A3 durante l’infezione, offrendo risultati che consentiranno di migliorare la valutazione del rischio di pandemia e di identificare nuovi bersagli antivirali.

Obiettivo

Avian influenza viruses (AIV) pose a constant socio-economic threat to humanity due to their potential to cause novel pandemics. This risk is underscored by recent reports of mammalian species infected with highly pathogenic strains of AIV. To develop effective drugs and improve risk assessment, a detailed understanding of the molecular mechanisms of AIV infection is crucial.

AIV are typical emerging zoonotic pathogens capable of crossing into new species. This depends on two factors: i) the new host must support viral replication, and ii) restrictive factors that inhibit infection must be evaded. One significant barrier to AIV infections in humans is the limited activity of avian-adapted viral ribonucleoprotein complexes. These complexes consist of one genomic RNA segment, nucleoproteins, and a viral polymerase. Recently, the host factor BTN3A3 was identified as a critical restriction element for zoonotic AIV, influencing cross-species viral evolution. However, the exact mechanisms through which BTN3A3 restricts the virus, and how the virus evades this restriction, remain unclear.

This study involves structural investigations conducted directly within infected cells at nanometer resolution by in situ cryo-electron tomography, an approach that is significantly pushing beyond the current state-of-the-art thereby setting new paradigms in the understanding of molecular infection mechanisms. The primary objective is to elucidate how viral host-adaptation mutations evade BTN3A3 restriction with the overarching goals to i) improve pandemic risk assessment tools, ii) reveal new drug targets, and iii) serve as a proof-of-principle for studying restriction factors during infection with other zoonotic viruses.

This research will be conducted under the supervision of Dr. Petr Chlanda at Heidelberg University, where I will have access to world-class facilities and training opportunities, supporting my growth as an independent researcher.

Campo scientifico (EuroSciVoc)

Parole chiave

Programma(i)

Argomento(i)

Meccanismo di finanziamento

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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(si apre in una nuova finestra) HORIZON-MSCA-2024-PF-01

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Coordinatore

UNIVERSITATSKLINIKUM HEIDELBERG
Contributo netto dell'UE
€ 202 125,12
Indirizzo
IM NEUENHEIMER FELD 672
69120 Heidelberg
Germania
Regione
Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis
Tipo di attività
Higher or Secondary Education Establishments
Collegamenti
Costo totale
Nessun dato