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Novel mechanisms of early defense against virus infections

Novel mechanisms of early defense against virus infections

Objective

Virus-induced type I interferons (IFN) have classically been considered to constitute the first line of defense against virus infections However, recent work by us and others has identified early antiviral actions that occur independently of inducible type I and III IFN expression and sometimes even prior to IFN action (e.g. Iversen,...., Paludan. Nature Immunology, 2016; Paludan. Trends in Immunology, 2016). These discoveries challenge the current thinking in the field that IFNs constitute the first line of defense. Hence, there is an urgent need for more detailed understanding of the immediate antiviral defense mechanisms. Most importantly, we remain to identify key players in IFN-independent antiviral responses, we completely lack insight into the mechanisms that govern these responses, and we also lack information on the importance of this layer of defense in mice and humans. In accord with this, my proposal follows four aims: (i) Identification of mechanisms of virus detection at epithelial surfaces, (ii) elucidation of the role of tonic IFN signaling in antiviral defense, (iii) identification and characterization of novel restriction factors, and (iv) deciphering the mechanisms that govern induction of the first wave of IFNs at epithelial surfaces. In addition, I will also explore the interactions between the early antiviral actions. To achieve the goals, I will combine unbiased genome-wide screens with hypothesis-driven approaches, and will integrate molecular biology/genetics/biochemistry with advanced cell culture systems, animal science and analysis of patient material. Strong preliminary data have been generated for all four aims, and world-leading collaborations are in place, hence minimizing the risks, and allowing fast progress. Our findings will (i) change the thinking in innate immunology by uncovering a novel layer of antiviral defense and (ii) provide new avenues for therapeutic modulation of immune responses.
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Host institution

AARHUS UNIVERSITET

Address

Nordre Ringgade 1
8000 Aarhus C

Denmark

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 2 480 338

Beneficiaries (1)

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AARHUS UNIVERSITET

Denmark

EU Contribution

€ 2 480 338

Project information

Grant agreement ID: 786602

Status

Ongoing project

  • Start date

    1 December 2018

  • End date

    30 November 2023

Funded under:

H2020-EU.1.1.

  • Overall budget:

    € 2 480 338

  • EU contribution

    € 2 480 338

Hosted by:

AARHUS UNIVERSITET

Denmark