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FLUPOL


Biology, Target Search and Drug Discovery

Host-specific variants of the Influenza Virus Replication Machinery

EC contribution
: € 1 973 450
Duration
: 36 months
Starting date
: 01/01/2007
Instrument
: STREP
Keywords
: Influenza virus polymerase, viral replication, X-ray crystallography, cryo-electron microscopy, host-dependent mutations, ribonucleoprotein particle, high throughput screening
Project Number
: SP5B-CT-2007-044263

Summary:

We aim to understand how the influenza virus replication machinery adapts during interspecies transmission and to use this knowledge to provide new tools to combat potentially pandemic influenza outbreaks.

Problem:

Currently circulating H5N1 avian influenza viruses are lethal to man and could cause a devastating pandemic if they became transmissible between humans. It is therefore crucial to understand the mechanisms whereby influenza virus adapts from avian to human hosts. The best understood factors in inter-species transmission are certain characteristics of the surface glycoprotein, haemagglutinin. However, several recent studies have highlighted the importance for transmissibility of mutations in the proteins of the viral replicative machinery, in particular the polymerase which transcribes and replicates the viral RNA. We propose a comprehensive study of the molecular structure and function of the influenza virus polymerase with the aim of understanding how it adapts during inter-species transmission.

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