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1918 RBD D225G in Lung Cases in the United States
Recombinomics Commentary 10:27
November 23, 2009

Betsy McKay: I just wanted to follow-up on the question about the mutation in norway.  I wondered if you could talk a little bit more about is it possible that this mutation has produced a more virulent form and what has CDC uncovered through its own work? 

Anne Schuchat:  this mutation has been seen sporadically here and there around the world.  Sometimes it's been seen in patients who had very mild disease and sometimes it's been seen in people who had more severe or fatal disease.  And, of course, lots of virus without this mutation has been seen in the fatal as well as the milder forms of H1N1 influenza.  There's some theoretical reasons why this particular mutation might lead an influenza virus to live easier in the deep part of the lungs and cause lower respiratory infections, but we've actually seen lower respiratory infections in a severe viral pneumonia without this mutation.  So I think it's too soon to say what this will mean long term.  It's an important finding and they're looking into it, but I don't think it has the public health implications that we would wonder about.  Did you have a second question?  Oh, what have we seen so far?  I believe it's been seen in the U.S. But associated with mild disease.  I believe.  I might need to verify that.  Do we have another from the room?  Okay.  We'll go back to the phone. 

The above comments are from the latest CDC update and regard the receptor binding domain change, D225G, which has recently been reported in Ukraine and Norway.  This change was also identified in 1918 and 1919 fatal lung cases and the change has been targeted in receptor binding domain studies.  These studies showed that the 1918 H1N1 with D225G was able to bind to gal alpha 2,3 and gal alpha 2,6, in contrast to the 1918 sequences with wild type D225, which targeted alpha 2,6.

Recent studies have also demonstrated that alpha 2,3 receptors are on alveolar epithelial type II cells, which regulate lung surface tension as well as immunological defenses which include the release of cytokines.  Binding of H1N1 to these cells could have significant clinical implications, which is supported by the recently published sequences which identifies D225G in lung and trachea samples form fatally infected patients.  The cases in Ukraine were also linked to hemorrhagic disease and the CDC sent out a warning on such cases due to sporadic reports in the United States.

The above response fails to note the identity between the receptor binding domain change in Norway and Ukraine and responses to that alert.  Moreover, media reports on fatal cases that develop ARDS in association with hemorrhagic disease in the United States continue to increase.

Details on the number and location of cases reported in response to the CDC alert would be useful.

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