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Efficient H5N1 Transmission Via Receptor Affinity Changes
Recombinomics Commentary
February 16, 2006
The potential acquisition of G228S by H5N1 offers several interesting possibilities. Sequence data suggest some H5N1's have the S227N changes while others do not. The sequence homology with H1N1 in swine is downstream from the S227N change, so the sequence is the same in isolates with and without S227N. Therefore, acquisition of G228S could create isolates that have SS at positions 227 and 228, while others would have NS at those two positions.
S227N has been shown to increase the affinity for human receptors in H5N1 isolates with that change. Increases in affinity are also seen in H3 which has S at positive 228. However, H3 also has S at position 227, so H5N1 without S227N would have SS at both positions if G228S was acquired.
Thus, acquisition of G228S could create two versions of Qinghai H5N1 with increased affinities for human receptors. As H5N1 expands its geographical reach it accesses new regional influenza sequences that create novel polymorphisms. As H5N1 migrates out of Africa, it may already have some changes that define new donor sequences for acquisitions of polymorphisms that increase receptor binding (E190D, G225D, Q226L, S227N, and G228S).
Some of the donor sequences for E190D exist in H7 isolates from the past as well as current influenza B sequences.
As H5N1 expands its geographical reach, it also increases opportunities for new recombinations and new acquisitions.
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