Pandemic flu H1N1 can cause more severe lung infection than seasonal
21 September 2009
Pandemic swine flu can infect cells deeper in the lungs than seasonal
flu can, according to a new study published in Nature Biotechnology
this month. The researchers, from Imperial College London, say this
may explain why people infected with the pandemic strain of swine-origin
H1N1 influenza are more likely to suffer more severe symptoms than those
infected with the seasonal strain of H1N1.
They also suggest that scientists should monitor the current pandemic
H1N1 influenza virus for changes in the way it infects cells that could
make infections more serious.
Influenza viruses infect cells by attaching to bead-like molecules on
the outside of the cell, called receptors. Different viruses attach to
different receptors, and if a virus cannot find its specific receptors,
it cannot get into the cell. Once inside the cell, the virus uses the
cell's machinery to make thousands more viruses, which then burst out of
the cell and infect neighbouring ones, establishing an infection.
Seasonal influenza viruses attach to receptors found on cells in the
nose, throat and upper airway, enabling them to infect a person's
respiratory tract. The research, which was funded by the Wellcome Trust,
the Medical Research Council and the Engineering and Physical Sciences
Research Council, shows that pandemic H1N1 swine flu can also attach to
a receptor found on cells deep inside the lungs, which can result in a
more severe lung infection.
The pandemic influenza virus's ability to stick to the additional
receptors may explain why the virus replicates and spreads between cells
more quickly: if a flu virus can bind to more than one type of receptor,
it can attach itself to a larger area of the respiratory tract,
infecting more cells and causing a more serious infection.
Professor Ten Feizi, a corresponding author of today's paper from the
Division of Medicine at Imperial College London, said: "Most people
infected with swine-origin flu in the current pandemic have experienced
relatively mild symptoms. However, some people have had more severe lung
infections, which can be worse than those caused by seasonal flu. Our
new research shows how the virus does this — by attaching to receptors
mostly found on cells deep in the lungs. This is something seasonal flu
The researchers found that pandemic H1N1 influenza bound more weakly
to the receptors in the lungs than to those in the upper respiratory
tract. This is why most people infected with the virus have experienced
mild symptoms. However, the researchers are concerned that the virus
could mutate to bind more strongly to these receptors.
"If the flu virus mutates in the future, it may attach to the
receptors deep inside the lungs more strongly, and this could mean that
more people would experience serious symptoms. We think scientists
should be on the lookout for these kinds of changes in the virus so we
can try to find ways of minimising the impact of such changes," added
The researchers compared the way seasonal and pandemic H1N1 flu
viruses infect cells by identifying which receptors each virus binds to.
To do this, the researchers used a glass surface with 86 different
receptors attached to it, called a carbohydrate microarray. When viruses
were added to the glass surface, they stuck to their specific receptors
and the corresponding areas on the plate 'lit up'. This meant the
researchers could see which receptors the different viruses attached to.
Pandemic H1H1 influenza could bind strongly to receptors called α2-6,
which are found in the nose, throat and upper airway, and it could also
attach more weakly to α2-3 receptors, which are found on cells deeper
inside the lungs. However, seasonal H1N1 influenza could only attach to
"Receptor binding determines how well a virus spreads between cells
and causes an infection," said Professor Feizi. "Our new study adds to
our understanding of how swine-origin influenza H1N1 virus is behaving
in the current pandemic, and shows us changes we need to look out for."
1. Robert A Childs, Angelina S Palma, Steve Wharton, Tatyana
Matrosovich, Yan Liu, Wengang Chai, Maria A Campanero-Rhodes, Yibing
Zhang, Markus Eickmann, Makoto Kiso, et al. Receptor-binding specificity
of pandemic influenza A (H1N1) 2009 virus determined by carbohydrate
microarray. Nature Biotechnology 27, 797-799 (September 2009)
doi:10.1038/nbt0909-797 Opinion and Comment
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