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.