Second mutation in Turkey H5N1 virus suggests adaptation to humans

Jan 19, 2006 (CIDRAP News) – A new report in Nature cites more evidence that mutations detected in H5N1 avian influenza viruses recovered from patients in Turkey may better equip the viruses to infect humans.

The World Health Organization (WHO) announced a week ago that a mutation in one virus sample could improve the virus's ability to spread from birds to humans. The mutation is believed to make the virus more likely to bind to human cell receptors and less likely to bind to avian cell receptors, the WHO said.

A news article published today by Nature says scientists have detected another mutation in the Turkish samples that may improve the microbe's ability to jump not only from birds to humans but also from human to human. However, a scientist quoted in the piece said the two mutations, on their own, are not likely to lead to efficient person-to-person transmission.

Virus samples from the first two Turkish children to die of avian flu have been analyzed at the National Institute of Medical Research (NIMR) in London. Last week the WHO announced that a sample from one of the patients had an amino acid change in hemagglutinin, the surface protein that enables flu viruses to bind to and enter host cells.

The same mutation was seen in two patients in Hong Kong in 2003 and in Vietnam last year, the WHO said. Previous research indicated that the Hong Kong 2003 viruses prefer human cell receptors over bird cell receptors, the agency said. But the WHO stopped short of suggesting that this would help explain the relatively high incidence of human cases in Turkey—at least 20 in about 2 weeks.

The Nature report, by Declan Butler, says the virus samples from both Turkish patients have a mutation in the polymerase protein, which serves to replicate the virus's genetic material. The change is a substitution of lycine for glutamic acid at position 627. The same mutation has been seen before, including in Eurasian poultry recently and in the one person who died in the 2003 outbreak of H7N7 avian flu in the Netherlands.

"The polymerase mutation is one of the ten genetic changes that gave rise to the 1918 pandemic flu virus," the story says. The mutation indicates adaptation to humans, said Alan Hay, director of the WHO flu laboratory at the NIMR, as quoted in the story.

The story goes on to say that the Turkish samples are the first in which the polymerase and hemagglutinin mutations have been found together. "They could make it easier for humans to catch the virus from poultry," it says. "But they might also favor human-to-human transmission." Together, the two mutations help the virus survive and infect cells in the nose and throat, increasing the chance that coughing would spread it via droplets, the story says.

However, Hay said it is hard to predict how the mutations will affect the virus's behavior and that "just two changes are unlikely to create efficient human-to-human transmission on their own," according to the report.

One other mutation—a change at position 153 of the hemagglutinin protein—also was found in one of the virus samples, the story said. Maria Cheng of the WHO told Nature it was unclear what effect that change has.

Michael T. Osterholm, PhD, MPH, director of the University of Minnesota Center for Infectious Disease Research and Policy, publisher of this Web site, said the findings point up how little is known about exactly what changes would be sufficient to produce a pandemic strain of virus.

"We know what changes occurred in the 1918 virus, but is that the example or is that the model?" he said. "In other words, does it have to be exactly like that, or can it be a series of changes somewhat like that? We don't know if some changes are more important than others or if some changes have to happen together."

While virologists have learned a lot, "there's more that we don't know than we do know," Osterholm added. "The thing I think is concerning about the situation in Turkey is we continue to see the potential for mutations to occur, which in turn leads us to the possibility that all the wrong mutations might occur and result in a 1918-like experience."

See also:

Jan 12 WHO statement on analysis of H5N1 virus from Turkish patients
http://www.who.int/csr/don/2006_01_12/en/index.html

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