# 3714
An interesting study in the current issue of Nature Biotechnology which helps explain why, in a small percentage of novel H1N1 infections, patients experience severe deep lung infections.
It all has to do with how this virus binds to receptor cells.
The receptor binding domain (RBD) of an influenza virus is that area of its genetic sequence that allows it to attach to, and infect, host cells.
Much like a key into a padlock, the RBD must `fit' the host cell in order for it to bind.
(Very Simplified Illustration of RBDs)
A little science. I’ll try to be gentle.
Animal cell membranes are comprised of a lipid bilayer with lots of strands (or chains) of sugars (carbohydrates), proteins, and fat molecules poking through them.
These carbohydrate molecules, some being glycolipids (carbohydrate and fat) and others glyoproteins (carbohydrate and Protein), form a dense sugary coating to all animal cell membranes.
Since there are a lot of different sugars, there are a lot of combinations to be found. The most accessible of these sugars for a virus are the ones at the tips of these chains, where a special sugar called sialic acid is often found.
Now, not all sialic acid molecules are the same.
Essentially, they are identified by what molecules they are attached to, and how they are attached. It gets pretty complicated, but suffice to say there are two special sialic acid configurations that are of particular interest to us when dealing with Influenza; the α-2,3 and the α-2,6 combinations.
The α-2,6 receptor cells are commonly found in the upper airway of humans, while the α-2,3 receptor cells are most often found deep in the lungs.
One of the reasons that the H5N1 (bird flu) virus hasn’t managed to transmit efficiently from human-to-human is because it is adapted to the kind of receptor cells most commonly found in the digestive tract of birds; the α-2,3 - not the α-2,6 receptor cells found in the human upper airway.
AI (Avian Influenza) viruses must make their way deep into the lungs to infect humans. And while it rarely happens, when it does, the resultant infection is generally far more severe than an upper airway infection.
Most human-adapted influenzas attach to the easy-to-reach α-2,6 receptor cells commonly found in nose, throat, and pharynx.
While 99% of novel H1N1 victims seem to experience relatively mild upper airway infections, an unlucky 1% see the infection go deeper into the lungs. Helen Branswell of the Canadian Press wrote about this phenomenon about a week ago, which I covered in a blog called Pathology Of Fatal H1N1 Lung Infections.
Lung damage in fatal swine flu cases more bird flu than seasonal flu: expert
By Helen Branswell Medical Reporter (CP)
TORONTO — The lungs of people who have died from swine flu look more like those of the victims of H5N1 avian influenza than those of people who succumb to regular flu, the chief of infectious diseases pathology at the U.S. Centers for Disease Control says.
Today, in a study that appears in Nature Biotechnology, we learn that researchers have determined that the novel H1N1 virus has the ability to infect both upper respiratory α-2,6 receptor cells, and to a lesser extent, the deep lung α-2,3 cells.
Which makes novel H1N1 a versatile virus, indeed.
Receptor-binding specificity of pandemic influenza A (H1N1) 2009 virus determined by carbohydrate microarray - pp797 - 799
Robert A Childs, Angelina S Palma, Steve Wharton, Tatyana Matrosovich, Yan Liu, Wengang Chai, Maria A Campanero-Rhodes, Yibing Zhang, Markus Eickmann, Makoto Kiso, Alan Hay, Mikhail Matrosovich & Ten Feizi
doi:10.1038/nbt0909-797
This paper isn’t open access, but the Medical Research Council (which partnered to fund this research) has an overview of the paper, and an interview with Professor Ten Feizi, a corresponding author of the paper.
Professor Feizi, in the accompanying article, expresses the concern that:
"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 Professor Feizi.
Pandemic flu can infect cells deep in the lungs, says new research
10 September 2009
Pandemic swine flu can infect cells deeper in the lungs than seasonal flu can, according to a new study published today in Nature Biotechnology. The researchers, funded by the Medical Research Council, Wellcome Trust and Engineering Physical Sciences Research Council, 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 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.
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