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Commentary
D225G Low Reactor In Washington State
Recombinomics
Commentary 20:30
April 7, 2010
In the US, the CDC had designated five isolates as low reactors, and all five have a change at position 159 (N159D, N159S, N159K). The CDC also designated an isolate from Germany, A/Bayern/59/2009 as a low reactor, and it also had only one non-synonymous change, G158E. Another isolate from Germany, A/Bayern/62/2009, also had the same non-synonymous change, and was designated a low reactor by Mill Hill.
Position 158 and 159 are in the same antigenic site, as is position 157. A study of pH1N1 escape mutants identified changes at position 157 (K157E and K157Q) and 158 (G158E), suggesting multiple changes at position 157 will impact neutralizing antibodies, suggesting K157N will also generate low reactors.
The finding of D225G with G158E was been seen in Russia and Italy, raising concerns that these combinations will be more common. The reporting of a sequence from Washington state with D225G and a change at a low reactor site increases those concerns.
The CDC did not designate A/Washington/58/2009 as a low reactor, but all CDC designated low reactors in the US have had changes at position 159, raising concerns about the ability of the current CDC antigenic characterization test to identify low reactors without a position 159 change.
The CDC has also discounted the significance of D225G, although a study from Norway identified 11 isolates with D225G and all were in severe or fatal cases. Similarly, virtually all isolates from Ukraine were from fatal cases, and D225G was in two of five sequences from fatal cases in 1918/1919.
The finding of D225G in association with an additional likely low reactor polymorphism, continues to increase pandemic concerns.
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