Ukraine Dead Increase to 344 – Sequences Released! RBD D225G in China and Australia Raise Ukraine Concerns! RBD Change D225G Confirmed in Ukraine!

• Looks like the A/H1N1 has indeed mutated to something more deadly in the RBD change to D225G.
   
  Recombinomics Commentary 19:17
  November 17, 2009
   
  1,502,345 Influenza/ARI  (+44,781)
  85,904 Hospitalized  (+2,378)
  344 Dead  (+16)
   
  The above tally is from the latest update from the Ukraine Ministry of Health.  The 344 dead represents an increase of 16 from yesterday’s total, which is similar to recent daily increases (see map).  The steady climb in fatal cases highlights the importance of the release of sequences by Mill Hill a WHO regional center in London.
   
  Included in the sequences from 10 isolates were four HA sequences with the receptor binding domain change, D225G, which was found in the one throat and three lung samples.  The change was not found in isolates from nasopharyngeal washes, suggesting D225G may lead to high concentrations of H1N1 in patient’s lungs.  The high concentration of virus leads to a cytokine storm that destroys the lungs in a few days.
   
  The finding of D225G in lung tissues raises concerns rergarding sequencing of isolates from nasopharyngeal swabs.  The monitoring of this important genetic change in the receptor binding domain may require sampling of lung tissues or fluids. The relationship between the negative nasopharyngeal washes and the lung samples would be useful.
   
  Kudos to Mill Hill and WHO for the prompt release of the panel of H1N1 sequences from Ukraine patients.
   
  RBD D225G in China and Australia Raise Ukraine Concerns
  Recombinomics Commentary 14:41
  November 18, 2009
   
  The recent outbreak in Ukraine has raised concern that receptor binding domain changes are responsible.  Although WHO has issued a new Ukraine situation update and has addressed preliminary changes in a news conference, they have not rule out receptor binding domain changes, and the recent announcement of investigations by two WHO Regional Centers (NIMR in Mill Hill, UK and CDC in Atlanta GA) suggests single nucleotide changes are under investigation.
   
  One such change is the receptor binding domain polymorphism D225G which is present on recently released sequences from China and Australia.  The HA sequence from China, A/Zheijiang/DTID-ZJU03/2009, is virtually identical to two earlier sequences from Yiwu (A/Zhejiang/DTID-ZJU02/2009 and A/Zhejiang-Yiwu/11/2009) and all were collected in September and appear to be from the same patient or contacts.  The patient eventually recovered, but was seriously ill and hospitalized for several weeks.  However, the three sequences from Yiwu match (see list here) sequences from an isolate, A/Hangzhou/1/2009, that is in another location in Zheijiang (see map), indicating D225G was appended onto the Hangzhou genetic background via recombination.
   
  A sequence released Monday at GISAID by the WHO regional center in Australia, A/Sydney/2503/2009, also has D225G, but on a different genetic backbone.  The 5′ end of the gene matches isolates from Singapore and Japan (see list), which do not have D225G.  Thus, D225G is appended onto this background via recombination, but the background in Australia is distinct from the background in China.
   
  Similarly, the two genetic backbones described above are distinct for two isolates in Sao Paulo, which  were from fatal cases.  The lung isolates signal the jumping of D225G from one genetic backbone to another.  This concurrent acquisition has been described in H5N1, as well as the genetic hitchhiking of H274Y in seasonal H1N1.
   
  This jumping of the same polymorphisms form one background to another signals major changes, especially when the polymorphism “in play” is a receptor binding domain change, which is cause for concern.
   
  The recent activity in Ukraine raises concerns that similar changes are in play there….
    
  Receptor Binding Domain Change D225G Confirmed in Ukraine
  Recombinomics Commentary 14:41
  November 18, 2009
   
  Mill Hill has released a series of sequences from patients in Ukraine.  Four of the samples had the receptor binding domain change D225G.  Three samples were from lung, one from a throat swab.
  Samples with D255G are listed below
   
  A/Lviv/N6/2009   
  A/Lviv/N2/2009
  A/Ternopil/N11/2009
  A/Ternopil/N10/2009
   
  All HA samples also had a Ukraine specific marker that had been previously found in swine.

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