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RBD Change D225G in
Ukraine Lungs Raises Concerns
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.
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