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Commentary
Transmission
of N159I Low Reactor
H1N1 In Montana In 2010
Recombinomics
Commentary 17:50
August 05, 2010
The CDC has released a series of H1N1 sequences at GISAID, which included more than 80 HA sequences. The vast majority was collected in 2010, and most 2010 isolates were collected in between April and May. Almost 20% of the HA sequences had low reactor changes at positions 157-159, or D225G, or both sets of changes. Three patients had D225G and low reactor changes (A/St. Petersburg/204/2010, A/Saratov/07/2010, A/Florida/04/2010), which follows the release of sequences from China with D225G and G158E. D225G is associated with severe or fatal infections, so the coupling of these two sets of markers is cause for concern.
In addition to the above combinations, three sequences from Montana had N159I. Although N159I had not been reported previously in human pH1N1, the change was identified in a Minnesota swine isolate, A/swine/Minnesota/02979/2010, collected Feb 17, 2010. The human isolates may have been from the same family based on the age of the index case (27F) and two subsequent isolates (2F and 1F) which were collected on April 4 and 7 (A/Montana/01/2010, A/Montana/02/2010, A/Montana/03/2010 respectively). All three HA sequences were identical. Previously all isolates in the US that were designated as “low reactors” by the CDC had changes at position 159, but none had N159I. The presence of this change in an earlier 2010 swine isolate adds to the mounting data supporting swine as a reservoir for newly acquired pandemic H1N1 polymorphisms in humans.
The low reactor polymorphism at positions 157-159 are not included in the current pandemic vaccine target. G158E was considered because of its growth promoting properties of H1N1 in chicken eggs, but was eliminated because of the low reactivity with the vaccine directed against California/7. Many of the low reactors are detected as mixtures, so isolates grown on mammalian cells may under-represent the frequency of changes at positions 157-159. The same is true for D225G, so the levels of low reactor sequences, as well as those with D225G, may be markedly higher than reflected in sequences deposited in databases, since most sequence are from isolates grown on mammalian cells.
The dramatic increase in 2010 with low reactor sequences as well as D225G raises concerns that prior vaccination or infection by H1N1will offer limited protection against these emerging variants, and an increase in the frequency of D225G can significant increase the number of severe and fatal cases this season, leading to a significant strain of health care delivery worldwide.
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