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 (ScienceNOW, 9 February). 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.
Previous work indicates that the human cell receptors the mutated H5N1 could target are present in the upper respiratory tract. This sets the stage for the virus to be spread among humans through coughing and sneezing, says Kawaoka.
"It's an important finding because it shows the possible molecular and structural basis for differences in viral attachment patterns," says Thijs Kuiken, a pathologist at Erasmus University in Rotterdam, the Netherlands, who has been studying how the H5N1 virus crosses the species barrier. But he is cautious about the implications for a pandemic. "The fact that the virus attaches to a particular receptor on a cell does not immediately mean that it can replicate in that cell," he says.
Kawaoka agrees that additional mutations are probably needed for the virus to acquire pandemic potential. "The problem is we don't know how many steps away a pandemic strain is," he says.