The high-resolution image of an influenza virus protein is published in by EMBL in Nature Structural and Molecular Biology

 A high-resolution image of an influenza virus protein could help researchers to develop new antiviral drugs with potential applications in veterinary and human medicine.

Structural biologists at the European Molecular Biology Laboratory (EMBL) are studying the virus at the molecular level to better understand how the influenza virus takes over the machinery of infected cells. In the current issue of the journal Nature Structural and Molecular Biology, they publish an image of a key protein domain that allows the virus to multiply by hijacking the protein production mechanisms of its host cell. The research opens up a new target for antiviral drugs that could be used to combat future influenza pandemics.

When the influenza virus infects a host, it starts to multiply in the host's cells. The viral polymerase protein is crucial in this process, as it copies the genetic material of the virus, allowing it to replicate. One component of the polymerase, called PB2, steals an important tag from host cell RNA molecules to direct the protein production machinery towards the synthesis of viral proteins. Research teams lead by Dr Stephen Cusack and Dr Darren Hart at the EMBL in Grenoble, France, have identified the PB2 domain responsible for binding the tag.

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"Viruses are masters of cunning when it comes to hijacking the normal functioning of the host cell," said Dr Cusack. "The influenza virus steals a password from the host messenger RNAs, molecules that carry the instructions for protein production, and uses it to gain access to the cell's protein-making machinery for its own purposes."

This "password" is a short piece of RNA called a "cap", which must be present at the beginning of all messenger RNAs (mRNAs) to direct the cell’s protein synthesis machinery to the starting point. The viral polymerase binds to the host cell's mRNA via its cap, cuts the cap off and adds it to its own mRNA. The viral mRNA can then be recognized by the host cell's machinery, allowing viral proteins to be made instead of host cell proteins.

The image generated by the EMBL researchers shows for the first time the individual amino acids responsible for PB2 cap binding. Collaborators at the National Biotechnology Center in Madrid, Spain, showed that disruption of the structure prevents the influenza virus from replicating.

"These findings suggest that the PB2 cap binding site is a very promising target for anti-influenza drugs," said Dr Hart. "Our new structural insights will help us design mimics of the cap that could inhibit viral replication and hence reduce the spread of the virus and the severity of the infection."

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