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RBD Change D225G in Ukraine Lungs Raises Concerns
Recombinomics Commentary 21:53
November 18, 2009

Mill Hill, a WHO regional center in London has placed sequences from 10 isolates from Ukraine (see map) on deposit at GISAID (see list below).  They are to be commended for the prompt deposit of these important sequences.  The availability of the sequences should put an end to wild speculation on the origins of the Ukraine outbreak. 

All H and N sequences are typical for H1N1, as indicated in early WHO announcements.  There are no large changes.  Additional gene segments have been deposited from a subset of these isolates (but not analyzed below).  There are silent changes that are in all or most Ukraine sequences, but the only HA polymorphism was the receptor binding domain change, D225G.  This polymorphism was in the three lung, as well as the one throat sample.  It was not in the nasopharyngeal washes or the isolate grown in MDCK cells suggesting the D225G may have a tissue tropism component and may allow for high levels of virus in the lung.

D225G was also found in necropsy lung tissue from fatal cases in Sao Paulo, further supporting tissue tropism associated with this polymorphism.  The polymorphism has recently appeared on a series of different genetic backgrounds, supporting acquisition by recombination. The genetic backgrounds were geographically diverse.  It was appended onto a genetic background specific for China as well as another distinct background found in Singapore and Japan.  It has also recently appeared on backgrounds from Spain and Brazil.  In addition, it was in isolates from last spring collected in the United States and Mexico.

The appearance of D225G on multiple recent genetic backgrounds raises concerns that the polymorphism is offering a selective advantage in association with multiple genetic backgrounds, and the selective detection of the polymorphism in lung and throat samples may indicate it is more widespread because of its absence from nasopharyngeal washes.  Lung and throat sampling may be required for detection and determination of the true geograpohical reach of this change..

More information on outcomes for these patients, as well as results for lung and nasopharyngeal samples from the same patient, would be useful.

The prompt release of these sequences should help guide further analysis of the evolving swine H1N1.

A/Khmelnitsky/1/2009    EPI_ISL_62017 
A/Ternopil/19/2009        EPI_ISL_62016 
A/Ternopil/11/2009        EPI_ISL_62015 
A/Ternopil/6/2009          EPI_ISL_62014 
A/Ternopil/5/2009          EPI_ISL_62013 
A/Lviv/N6/2009*             EPI_ISL_62012  
A/Ternopil/N11/2009*   EPI_ISL_62011 
A/Ternopil/N10/2009*   EPI_ISL_62010 
A/Lviv/N2/2009*             EPI_ISL_62009 
A/Kyiv/N1/2009              EPI_ISL_62008 

* D225G

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