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The CDC has recently released
(at GISAID) a large series of HA sequences from collections in
2010. Almost 20% of the more than 80 sequence had a change at
positions 157-159 or D225G. Three of the isolates had both and
all three were sequenced twice by the CDC. These isolates were
collected in February and March.
All had D225G in both sequences and the D225G was not present as a mixture. One sequence, A/St. Petersburg/204/2010 had K157E as a mixture in both sequences and both were designated as “low reactor” by the CDC. The other Russian isolate, A/Saratov/07/2010, had K157E and G158E in one sequence (both as mixtures with wild type), while the other sequence just had K157E. Both isolates were also designated as a “low reactor by the CDC. The third isolate, A/Florida/04/2010, had G158E as a mixture in both isolates, but neither was designated as a low reactor by the CDC. However, an earlier isolate from Germany with D158E was designated as a “low reactor” by the CDC. They have apparently changed their assay, at least for US isolates because all US isolates designated as a “low reactor” by the CDC have a change at position 159 (including the three recent isolates from Montana, although the CDC only designated two of the three sequences as low reactors, even though all three HA sequences were identical.
Others, including MedImmune, have noted that G158E sharply reduces the titer of their anti-sera against California/7, the pandemic target, and escape mutants also involved G158E, further linking G158E to a reduced titer against wild type pandemic H1N1. The combination of D225G with G158E was also reported in two recent isolates from China, as well as earlier isolates from Russia and Italy.
The latest sequences increase the number of pandemic H1N1 with D225G couple to changes at positions 157-159 and increase concerns that a variant with both sets of changes will emerge, leading to an increase in severe and fatal cases. Reports from India raise concerns that such changes are already appearing. Earlier sequences from fatal cases had D225G and media reports suggest D225G is also in isolates from recent fatal cases in India, where case fatality rates are remarkably.
The recently released sequences by the CDC continue to raise concerns of emerging variants with D225G.