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Innate immunity in influenza virus infection of mammalian airways

Objective

Emerging influenza A virus (FLUAV) infections pose a considerable health threat to mankind. The molecular determinants governing increased virulence of emerging virus strains in humans are presently not well known. We propose to identify and study the essential viral and host factors that determine the outcome of infection. FLUAV enters the human respiratory tract and must replicate in the face of multiple innate immune defence mechanisms to establish infection in vivo. Successful viruses must adapt to intrinsic cellular restriction factors and evolve the capacity of circumventing the antiviral interferon (IFN) response, either by limiting IFN production or by blocking IFN actions.

We will test the hypothesis that the speed and efficiency by which a given virus circumvents these early host responses are critical determinants in its host range and pathogenicity. In this respect, the crucial role of the virus polymerase and its cellular interactors will be analysed. Likewise, the importance of the IFN-inducible Mx GTPase as a major anti-FLUAV effector molecule will be evaluated. Virus-induced inflammatory cytokines and chemokines exert powerful effects against FLUAV in lung epithelial cells.

However, they may be detrimental to the host, causing accelerated influenza pathogenesis in the human respiratory tract. We will analyse viral factors governing the innate antiviral cytokine response and determine the impact of these factors on virus growth, cell survival and pathogenicity. Human, avian and porcine FLUAV will be used in animal models and in cell culture systems, such as human airway epithelium. The present studies should generate important information that will help to better understand the processes involved in the emergence of lethal influenza viruses and to develop efficient control measures against these devastating pathogens.

Call for proposal

FP6-2005-SSP-5-B-INFLUENZA
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Funding Scheme

STREP - Specific Targeted Research Project

Coordinator

ALBERT-LUDWIGS-UNIVERSITÄT FREIBURG
Address
Fahnenbergplatz
Freiburg
Germany

Participants (8)

NOVARTIS VACCINES AND DIAGNOSTICS S.R.L.
Italy
Address
Via Fiorentina 1
Siena
UNIVERSITEIT GENT
Belgium
Address
Sint-pietersnieuwstraat 25
Gent
THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
United Kingdom
Address
University Offices, Wellington Square
PO Box 9600 Oxford
INSTITUT PASTEUR
France
Address
25 Rue Du Dr Roux
Paris
FONDAZIONE HUMANITAS PER LA RICERCA
Italy
Address
Via Manzoni, 56
Rozzano (Mi)
SHANGHAI INSTITUTES OF BIOLOGICAL SCIENCES, CHINESE ACADEMY OF SCIENCES
China
Address
320 Yueyang Road
Shanghai
ALTA RICERCA E SVILUPPO IN BIOTECNOLOGIE SRL - ALTA SRL
Italy
Address
Via Fiorentina 1
Siena
PHILIPPS-UNIVERSITÄT MARBURG
Germany
Address
Biegenstrasse 10
Marburg