New findings, reported in today in the online open access journal Respiratory Research, about how the virus binds to the respiratory tract and lung suggest children may be particularly susceptible to avian influenza,. The results also mean that previous receptor distribution studies may have to be re-evaluated.
John Nicholls and colleagues at the University of Hong Kong and Adelaide Women and Children's Hospital, in Australia, describe a modified technique to visualize the putative receptors for influenza viruses in the upper and lower respiratory tract, including the lung.
Sialic acid molecules on the cell surface act as chemical beacons for the influenza virus. Once the virus finds sialic acid, it can attach and infect the cell, although the precise distribution of sialic acid molecules affects how easily the virus can find host cells to infect.
The team has turned to lectins- molecules which bind sugars, to help them differentiate receptors for human and avian influenza viruses. The researchers used an improved staining technique to see how well two lectins, Sambucus nigra agglutinin (SNA) and Maackia amurensis agglutinin (MAA), bind to different forms of sialic acid on respiratory tract cells in healthy adults and children. SNA is particularly good at identifying the receptor for human influenza viruses while MAA identifies the receptor for avian viruses - including H5N1.
The researchers found that a particular form of MAA (MAA1) displayed widespread binding throughout the respiratory tract, but was particularly good at binding to children's cells in the lower respiratory tract as well as the upper respiratory tract of adults. Although this MAA1 binding is not unique for avian influenza receptors, these findings could explain how avian influenza infects children more readily than it does adults. This may explain previous findings from this group that avian H5N1 viruses can infect the human upper respiratory tract, even though these tissues were thought to lack receptors for these viruses.
"Understanding the how and why of avian virus infection of humans is a very complex process involving research into properties of H5N1 virus, the host receptor and the cellular response" said Dr John Nicholls. "We believe that the studies we have done investigating where the receptors are located and their distribution with age is a small step towards unravelling this process and help in finding ways to diminish the potential treat from this emerging infection."
Sialic acid receptor detection in the human respiratory tract: evidence for widespread distribution of potential binding sites for human and avian influenza viruses
John M Nicholls, Anthony J Bourne, Honglin Chen, Yi Guan and J S Malik Peiris
Respiratory Research (in press)
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