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WHO Confirms D225G in Lung Cases in Norway and Ukraine
Recombinomics Commentary 23:50
November 20, 2009

Norway reported finding a mutated virus in three people who died or were severely ill. The mutation, known as D222G on the receptor binding domain, allow the virus to grow deeper in the lungs.

The mutation does not appear to be circulating and may have spontaneously arisen in the three patients, said Geir Stene-Larsen, director of the Norwegian Institute of Public Health. Only 3 of Norway's 70 tested samples had it.

Asked about that, Dr. Schuchat said the same mutation had also been found in mild cases in several countries, and it did not make the virus resistant to vaccine or to treatment with drugs like Tamiflu. She said she did not want to "underplay" it, adding that "it's too soon to say what this will mean long term."

The D222G mutation allows the virus to bind to receptors on cells lining the lungs, which are slightly different from those in the nose and throat. Henry L. Niman, a flu tracker in Pittsburgh, has been warning for a week that D225G - the same mutation under a different numbering system - has been repeatedly found in Ukraine, which is in the grips of a severe outbreak and where surprising numbers of people have died with lung hemorrhages - the kind of pneumonia that can be caused by an immune system's "cytokine storm" attacking a new virus.

The above comments from the Donald McNeil update in tomorrow's New York Times are the first direct acknowledgement that the receptor binding domain change in Norway and Ukraine are the same.  Earlier the WHO had put out an update on the change in Norway and noted that a similar change had been seen elsewhere, and included Ukraine in the list of countries.

In earlier Ukraine updates WHO did not acknowledge any receptor binding domain changes, but the sequences released at GISAID by Mill Hill had D225G in four of the ten HA sequences, which precisely matched the four fatalities, raising concern that the previously described "destruction of both lungs" was driven by the acquisition of D225G.  The group in Norway also found the change in dead or dying patients, further supporting a significant role of this change the the cytokine storm associated with this acquisition.

This change has been reported in a number of recently described cases including two fatal cases in Sao Paulo, a seriously ill case in China, and cases in Sydney, Australia and Vladivostok.  The polymorphism had also been seen in earlier isolates in the United States, Mexico, Spain, and Japan.

The role of this change in fatal cases may be dependent on the viral load. The cytokine storm is precipitated by high levels of virus, and lower levels may produce milder disease.

The above report, noting the identity between Norway and Ukraine should lead to more detailed analysis of tissue samples from fatal cases, which may contain an increased frequency of D225G, a receptor binding domain change identified in 1918 and 1919 samples.

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