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
Designer cells: artificial enzyme can activate a gene switch
22.05.2018 | Universität Basel
Flow of cerebrospinal fluid regulates neural stem cell division
22.05.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.
At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...
There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?
At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...
So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics
Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...
The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...
A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.
The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...
02.05.2018 | Event News
13.04.2018 | Event News
12.04.2018 | Event News
22.05.2018 | Life Sciences
22.05.2018 | Earth Sciences
22.05.2018 | Trade Fair News