EU-funded study finds pandemic swine flu infects cells deep inside lungs
Which type of flu infects cells deep inside the lungs: pandemic swine or seasonal? EU-funded researchers say pandemic swine flu wins hands down. Published in the journal Nature Biotechnology, the findings of a new study suggest that humans infected with the pandemic strain of swine-origin H1N1 influenza will probably experience more severe symptoms than patients infected with the seasonal strain of H1N1 because of how the swine virus attaches to specific receptors in the body.
The study was funded in part by the FLUPATH (Avian influenza: impact of virus-host interactions on pathogenesis and ecology) and FLUINNATE (Innate immunity in influenza virus infection of mammalian airways) projects under the 'Policies support' activity of the EU's Sixth Framework Programme (FP6). Financial support amounts to EUR 1.92 million for FLUPATH and EUR 1.44 million for FLUINNATE.
This latest research, headed by Imperial College London in the UK, highlights that scientists should keep an eye on the current pandemic H1N1 influenza virus, especially for changes in how cells are infected, as they could trigger more serious infections.
So how do cells become infected? Scientists say influenza viruses attach to protein molecules on the cell's exterior. These molecules, called receptors, are embedded in either the plasma membrane or the cytoplasm of a cell. Each virus attaches itself to a specific receptor. When a virus fails to find its specific receptor, it also fails to enter the cell. But if a virus succeeds in entering the cell, it then manipulates the cell's machinery to produce the components that are needed to assemble new viruses. The viruses then leave the cell and infect other cells. The end result: infection.
The researchers from Germany, Japan, Portugal, Spain and the UK said seasonal influenza viruses attach to receptors located on cells in the nose, throat and upper airway. Once firmly established, they are able to infect a person's respiratory tract. The difference with the pandemic H1N1 swine flu is that these viruses find their way on cells deep inside the lungs and cause more serious infection.
Using a glass surface with 86 different receptors attached, the scientists were able to determine the specific receptors to which the viruses bind. Their work shows that pandemic H1H1 influenza could bind strongly to receptors called alpha2-6 that are located in the nose, throat and upper airway, as well as to alpha2-3 receptors, located deeper inside the lungs. Seasonal H1N1 influenza, they observed, attaches only to alpha2-6 receptors.
"Most people infected with swine-origin flu in the current pandemic have experienced relatively mild symptoms," explained Professor Ten Feizi of The Glycosciences Laboratory at Imperial College London. "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 cannot do."
Based on their research, the team found that pandemic H1N1 influenza bound weakly to the receptors in the lungs compared to the receptors in the upper respiratory tract. It is because of this that the majority of infected people suffer from mild symptoms. But the scientists believe 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," stated Professor Feizi. "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."
"Receptor binding determines how well a virus spreads between cells and causes an infection," Professor Feizi pointed out. "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 for."
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