Cryomicroscopy shows how flu virus fuses with host cell

Scientists at the Francis Crick Institute have visualised how the influenza virus fuses with the membrane of a host cell. This is an essential step in the virus's lifecycle and the findings could lead to new approaches to prevent infection. 

Peter Rosenthal of the Crick said: "The influenza virus is an important human pathogen and understanding all the steps in its lifecycle are important for understanding virus infection. Entry into the host cell is a key step in virus infection.

"During infection, the virus delivers its genome into the host cell by fusing its own lipid membrane with that of the host cell membrane. This process is achieved by structural changes in the hemagglutinin, which is one of two protein spikes on the virus surface. The hemagglutinin spikes insert into host cell target membrane and mediate the close approach and fusion of membranes."

Lesley Calder, the first author of the study, used cryomicroscopy, a high-resolution imaging method, to observe how the virus fuses with a target membranes in the laboratory.

Cryomicroscopy images biological structures in a frozen-hydrated state that preserves high-resolution features. Images are then acquired via an electron microscope using minimal electron exposure so that the electrons do not damage the structures of interest. This technique allowed the scientists to record images from many angles and to calculate 3D maps of the virus fusing with the target membranes. The 3D maps, combined with information from previous biochemical and structural studies, provide an explanation of how membrane fusion occurs.

Dr Rosenthal said: "By imaging at high-resolution the way the virus fuses with a membrane, we can learn how the viral proteins and their structural changes bring about membrane fusion.

"The more detailed understanding of this process identifies steps that could be blocked and may therefore provide new targets for drugs designed to inhibit these steps in the future."

The paper, 'Cryomicroscopy provides structural snapshots of influenza virus membrane fusion', is published in Nature Structural and Molecular Biology.

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