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Michigan H3N2v Cases With PB1 E618D and H1N1pdm09 M Gene
Recombinomics Commentary 21:45
October 4, 2012

The CDC has released a large series of H3N2v sequences from August, 2012 cases, increasing the number of July/August sets to 90.  Included were two sets of sequences from two cases in Michigan collected on August 16.  Sequences from one case, A/Michigan/20/2012, cover seven of the eight gene segments (all except NS), while the second set, A/Michigan/19/2012, from an adult (54M), covered PB1 and PA.  The shared sequences were virtually identical suggesting all 8 gene segments match.  Both PB1 sequences had E618D and were closely related to sequences from 2010 human cases, as was seen in recent swine sequences from June collections in Ohio (A/swine/Ohio/1/2012, A/swine/Ohio/6/2012, A/swine/Ohio/7/2012).

As seen in the Ohio swine sequences, the N2 was closely related to sequences from the first 10 cases in 2011 and were from a lineage found in H1N2 swine.  Moreover, these sequences also had an H1N1pdm09 M gene as well as an H3 gene that was related to human H3N2v sequences from US cases (2009-2012).

The presence of PB1 E618D and H1N1pdm09 M genes in the Ohio swine sequences raised concerns of increased human adaptation, although prior to the release of the Michigan sequences, this combination had not been reported in humans.  All 2012 cases had an H1N1pdm09 M gene, but none had PB1 E618D or the N2 lineage seen in early 2011 cases.  Instead, all had an N2 lineage that circulated in H3N2v swine and was first seen in human H3N2v in sequences from the West Virginia day care center (
(A/West Virginia/06/2011 and A/West Virginia/07/2011).

The presence of PB1 E618D in two cases in Michigan raises concerns of increased transmission.  Michigan reported 5 cases in August and sequences from the first case, A/Michigan/14/2012, was similar to other 2012 H3N2v cases.  However, Michigan has announced a sixth case which has been “under investigation” for several weeks (as noted in the past 3 Michigan flu updates for weeks 36-38).  More information on this case and other cases “under investigation” would be useful.

The two cases with PB1 E618D and an N2 gene found in 2011 cases once again highlights the discordance between human and swine cases.  The N2 gene found in the two 2012 Michigan cases are widespread in swine (including the 4 June cases in Ohio), yet all other reported human H3N2v cases in 2012 have the N2 lineage found in the West Virginia outbreak.  Prior to the explosion of cases in July and August, swine with this N2 as well as H3 and MP which matches the human cases was limited to two examples (in North Carolina and Indiana).

The limited number of human cases with the N2 that is widespread in swine suggests that jumps from swine to human are relatively rare, but the two newly released sequences from Michigan raises concerns that the spread of this novel constellation may be increasing.

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