Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

A first glimpse of the influenza replication machine

26.02.2007
The first 3D structure from a key influenza protein sheds light on transmission of flu between birds and humans

In 1918, 50 million people died during a worldwide influenza pandemic caused by mutation of a bird-specific strain of the influenza virus. Recently H5N1, another highly infectious avian strain has caused outbreaks of bird flu around the world. There is great concern that this virus might also mutate to allow human-to-human transmission and cause another catastrophic pandemic.

Specific mutations in a viral protein, the polymerase, contribute to the ability of the bird virus to jump the species barrier to humans. Researchers from the European Molecular Biology Laboratory (EMBL) in Grenoble and Heidelberg, the Institut de Biologie Structurale (IBS) and the Unit of Virus Host Cell Interactions (UVHCI)*, both in Grenoble, have now produced the first 3-dimensional image of part of this key protein. The study, which is published in the current issue of Nature Structural and Molecular Biology, investigates the structure and function of the protein and sheds light on how polymerase mutations contribute to transmission of avian flu to humans.

Upon infection the influenza virus starts multiplying in the cells of an infected host. The polymerase is crucial in this process because it copies the viral genome and directs the production of its proteins. Interfering with polymerase function would prevent the virus replicating, thereby reducing the spread of the virus and the severity of the infection.

“For many years scientists have tried to understand the flu polymerase and to look for weak points that could be targeted by drugs,” says Darren Hart, whose team participated in the research at EMBL Grenoble. “But no one could get enough protein to analyse its structure. We developed a way to use robots to screen tens of thousands of experimental conditions and discovered a piece of the influenza polymerase that we could work with. It is a small part of the entire protein, but it provides interesting insights into how the protein works and how mutations may affect host range.”

Together with scientists at the IBS they visualized the atomic structure of the protein and discovered a previously overlooked signal that labels it for transport to the human nucleus where the genetic material of the virus is replicated. Cell microscopy studies at EMBL Heidelberg revealed that the human nuclear transport protein, importin alpha, recognises this signal and shuttles the polymerase into the nucleus. To find out how the polymerase and importin interact, Stephen Cusack, head of EMBL Grenoble, and collaborators at the UVHCI, used the high intensity X-ray source of the European Synchrotron Radiation Facility to generate a high-resolution image of the two proteins interacting with each other. The image revealed that mutations known to play a role in the transmission of avian influenza virus to mammals were located within, or close to, this site of interaction. This suggests that mutations may affect the efficiency of nuclear transport and through this the ability of the virus to replicate in different species.

“Interfering with polymerase function could provide new ways to treat or prevent flu,” says Cusack, “but this will require a detailed picture of the rest of the polymerase. This is what we are aiming for in our new FLUPOL project. In a joint effort with other European laboratories, and with financial support by the European Commission, we will explore both structure and function of this key drug target and try to characterise other mutations implicated in bird-to-human transmission.”

* The Unit of Virus Host Cell Interactions is a collaboration of the Centre National de la Recherche Scientifique (CNRS), the Université Joseph-Fourier in Grenoble and EMBL.

Anna-Lynn Wegener | alfa
Further information:
http://www.embl.org/aboutus/news/press/2007/25feb07/index.html

Further reports about: Grenoble Influenza Polymerase Transmission function

More articles from Life Sciences:

nachricht How brains surrender to sleep
23.06.2017 | IMP - Forschungsinstitut für Molekulare Pathologie GmbH

nachricht A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Quantum thermometer or optical refrigerator?

23.06.2017 | Physics and Astronomy

A 100-year-old physics problem has been solved at EPFL

23.06.2017 | Physics and Astronomy

Equipping form with function

23.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>