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Match Failures Between Swine and Humans
Sequences from 13 of the H3N2 isolates included the M gene, and six had an M gene from H1N1pdm09 (A/swine/Missouri/A01240017/2011, A/swine/Minnesota/A01240127/2011, A/swine/Illinois/A01243094/2012, A/swine/Illinois/A01203226/2012, A/swine/Iowa/A01203196/2012, A/swine/Iowa/A01203197/2012). However, none of the six had an H3 that matched the human sequences from 2011 or 2012.
Similarly, 29 H3 sequences were released, but only two 2010 isolates from Minnesota (A/swine/Minnesota/A01076999/2010 and A/swine/Minnesota/A01134337/2010) matched the human H3 sequences, but neither had an M gene from H1N1pdm09. Instead the M gene was similar to the swine H3N2 M gene in the human cases from 2010. Moreover, all eight gene segments for A/swine/Minnesota/A01076999/2010 were released, and they matched the human isolates A/Wisconsin/12/2010 and A/Pennsylvania/40/2010). The N2 from A/swine/Minnesota/A01134337/2010 also matched the human sequences suggesting that this isolate also matched the human sequences in all 8 gene segments.
Thus, the latest swine demonstrate a growing trend of swine sequences away from the human sequences. The evolution of the human sequences was seen in the first H3N2v isolate in the United States, A/Kansas/13/2009. Most of the internal genes were related to H1N1 from an outbreak at the Hudson County fair in 2007. However, the 2009 human sequence also had PB1 E618D, which was subsequently found in all 6 human cases in 2010. This match in PB1 also extended to the other human H3N2 isolates, which involved most of the genes from most of the human cases. This is demonstrated in clustering in the phylogenetic trees in the upcoming CDC publication, “Human Infections with Novel Reassortant Influenza A(H3N2)v Viruses, United States, 2011” which has H3 and M genes in Figure 1 as well as the other six gene segments in the supplement.
In 2011 the evolution was more dramatic. The first 10 human cases matched each other in all 8 gene segments, which had 5 genes from the 2010 human cases (PB2, PA, HA, NP, NS) as well as three genes from an H1N2 Ohio isolate, A/swine/Ohio/FAH10-1/2010, (PB1, NA, MP) which included an H1N1pdm09 M gene. Although the 10 human cases were from four states (Indiana, Pennsylvania, Maine, Iowa), only two matches were identified in swine (A/swine/NY/A01104005/2011 and A/swine/Iowa/A01202640/2011).
The last two cases in 2011 (A/West Virginia/06/2011 and A/West Virginia/07/2011) and the first case in 2012 (A/Utah/10/2012) acquired the N2 gene from a lineage circulating in H3N2v swine.
This constellation has not been identified in swine, in spite of enhanced USDA surveillance as demonstrated in the large number of recently released sequences.