The H5N1 virus, better known as bird flu, may have a way of becoming more dangerous to people. Researchers have identified two mutations in a surface protein of the virus that enable it to bind more easily to human cells. Watching for these mutations in viruses isolated from people could provide early warning of the emergence of a virus with pandemic potential.
Avian and human viruses differ in the types of receptor proteins they recognize. This has made human H5N1 infections thankfully rare--so far, there have been only 258 cases in 10 countries. Key to this discrimination is a protein known as hemagglutinin--the H in H5N1--which is tailor-made to bind to receptors on bird cells. It is thought that an avian influenza virus will only be able to infect people efficiently if the hemagglutinin protein mutates in a way that facilitates its binding to human cell receptors.
To search for such mutations, an international team led by Yoshihiro Kawaoka, a virologist at the University of Tokyo and the University of Wisconsin, Madison, screened viral samples collected from both birds and humans. This enabled the researchers to zero in on two single amino acid changes on the hemagglutinin molecule, each of which enables the virus to bind to human receptors. A structural analysis of these proteins found that the two amino acids are located in positions on the molecule where they could be involved in binding to host cell receptors. Both mutations were isolated from humans infected with the virus and were not present in any of more than 600 avian isolates checked, the group reports today in Nature.
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