The virus isolated from the second swine flu patient in the Netherlands has an intriguing mutation in a gene called PB2 that could mean that the virus has become better at spreading from person to person, a team of Dutch researchers reported on Friday on ProMED, a monitoring system for disease outbreaks. But they're the first to acknowledge that it could also be a red herring.
The virus isolated from the patient, a 53-year-old woman who developed the first symptoms flying home from Cancun, Mexico, on 30 April, has a change at position 677 of the gene for PB2, which encodes the virus's polymerase protein. As a result of the change, an amino acid called glutamic acid in the protein chain is replaced with another one called glycine.
This particular region of the PB2 gene has long piqued flu scientists' interest, says Marcel Jonges, a researcher at the Dutch National Institute for Public Health and the Environment (RIVM) in Bilthoven. Dozens of studies have suggested that a mutation at a nearby position—627—can make H5N1 avian flu viruses more virulent and more transmissible between humans. And last year, a study in PloS Pathogens hinted that a change at position at 677 could do the same. The Dutch patient, says Jonges, is the first case of swine flu in which the latter change has been seen.
Oliver Pybus of Oxford University, one of the authors on the PloS Pathogens paper, calls the findings "intriguing," but he cautions that the mutation could be meaningless. We need more lab studies, for instance in animals, to show that the mutation actually does make a difference, he says. Jonges agrees, and such studies are under way at the lab of influenza virologist Ron Fouchier at Erasmus Medical Center in Rotterdam, he says. "But we wanted to get this finding out as soon as possible, so other people can look for this, too," he adds.
Very little sequence data on PB2 has been gathered in the swine flu outbreak so far, Jonges says, because most scientists are focused on the genes for hemagglutinin and neuraminidase, the famous H and N that sit on the virus's outside. The PB2 gene hasn't yet been discussed on a new wiki-style page where Pybus and other scientists analyze genetic information about the swine flu outbreak as it comes in. More researchers should start sequencing the PB2 gene, says Jonges, and in particular the region between position 600 and 700 that seems to play a role in adaptation to human hosts.
—Martin Enserink
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