Researchers get closer to finding influenza virus' Achilles heel

London, May 5 : Researchers have created a high-resolution image of a key protein that enables influenza virus to multiply by hijacking the host cell protein production machinery. The researchers behind this achievement - structural biologists at the European Molecular Biology Laboratory (EMBL) and the joint Unit of Virus Host-Cell Interaction of EMBL, the University Joseph Fourier and National Centre for Scientific Research (CNRS), in Grenoble, France - say that their work may lead to the production of more effective medicines to combat future influenza pandemics.

The researchers say that the viral polymerase, the enzyme that copies its genetic material and helps to produce more viruses, is crucial to the multiplication of the influenza virus in the cells of its host.

They also say that one component of the polymerase, called PB2, plays a key role in stealing an important tag from host cell RNA molecules to direct the protein production machinery towards the synthesis of viral proteins.

Stephen Cusack and Darren Hart of EMBL Grenoble say that their team has identified the PB2 domain responsible for binding the tag, produced crystals of it, and examined them with the powerful X-ray beams of the European Synchrotron Radiation Facility (ESRF).

"Viruses are masters of cunning when it comes to hijacking the normal functioning of the host cell. The influenza virus steals a password from 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," Nature magazine quoted Cusack as saying.

In their study report, the researchers have revealed that the password is a short extra piece of RNA, a modified RNA base 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 study report says that the viral polymerase binds to host cell mRNA via its cap, cuts the cap off and adds it to the beginning of its own mRNA, a process known as 'cap snatching'.

According to the researchers, the capped viral mRNA can then be recognised by the host cell machinery allowing viral proteins to be made, at the expense of host cell proteins.

The researchers have also found that disruption of the PB2 cap-binding site prevents the influenza virus from replicating.

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

The research team has unveiled the high-resolution image of the protein domain in the journal Nature Structural and Molecular Biology.

ANI