First Glimpse Of Influenza Replication Machine

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Source: European Molecular Biology Laboratory
Date: February 26, 2007
Science Daily — 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."

http://www.sciencedaily.com/releases...0226101632.htm

Crystal structure of the influenza polymerase domain (red) interacting with the human protein importin »5 (blue) involved in nuclear transport. (Credit: Image courtesy of European Molecular Biology Laboratory)