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1918 RBD Polymorphsm
in Ukraine H1N1?
These changes are frequently linked to changes in the receptor binding domain (RBD) in the HA protein. Changes in this domain can affect affinity for receptors and also modify tissue tropism. The recent expansion of seasonal H3N2 with M2 S31N was linked to two changes in or near the receptor binding domain, S193F and D225N.
Recent isolates from Sao Paulo, Brazil, collected from necropsy tissue from fatal cases had two changes at position 225. Two of the isolates, A/Sao Paulo/53845/2009 and A/Sao Paulo/53838/2009) had D225N (see list), the same change seen in seasonal H3N2. Interestingly, the swine H1N1 is a triple reassortant with flu genes from swine, humans, and birds. The human gene is PB1 and it was acquired in swine infected with a human H3N2. The initial isolates had three human genes, the H3 and N2 as well as the PB1. Thus, the prior association of the human PB1 in isolates with human H3,may increase the advantage offered by D225N.
However, two other isolates from Sau Paulo, A/Sau Paulo/53225/2009 and A/Sau Paulo/53206/2009, collected from the lungs of fatal cases, had another change at position 225, D225G. This polymorphism is more widespread and recent isolates have been found in Japan, Spain, and China (see list ). Moreover this polymorphism has been found in two isolates from the 1918/1919 pandemic, A/New York/1/1918 and A/London/1/1919. Thus, in 1918 the H1N1 virus usually had a D at position 225, but some of the later isolates had D225G, which parallels the data from the 2009 swine H1N1 isolates.
These RBD changes in recent isolates from Sao Paulo, as well as the presence of D225G in sequences from 1918/1919 raise concerns that the swine H1N1 is adapting to its human host by acquisition of RBD polymorphisms.
The explosion of cases in Ukraine, and delays in the release of sequences from fatal cases in Ukraine is a cause for increasing concern. Recent accelerations of deaths have been widespread across the northern hemisphere, raising concerns that receptor binding domain changes described above, as well as a third polymorphism at position 225, D225E, (see list) are gaining traction as the swine H1N1 adapts to human hosts.
An update on the Mill Hill sequences and deposit of such sequences at a public database such as GISAID, where Mill Hill recently deposited sequences from Europe, would be useful.