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Genetic Instability In H1N1v Wisconsin Case
Recombinomics Commentary 03:30
December 28, 2011

The virus identified in Wisconsin has genes from avian, swine and human influenza viruses, making it a so-called “triple reassortant” (tr) virus. Triple reassortant viruses have been circulating in U.S. swine since the 1990s. However the virus detected in Wisconsin is different from earlier triple reassortant influenza A H1N1 viruses in swine (tr-H1N1) in that it has acquired the matrix [M] gene) from the 2009 influenza A (H1N1) virus.

The above comments are from the latest CDC “Haveyouheard?” and describe the first human trH1N1 (H1N1v) reported since the 2009 pandemic.  In the four years prior to the pandemic the CDC had reported 13 human cases involving triple reassortants, and 12/13 were trH1N1.  However, as noted this isolate has a number of “firsts” for human cases.
The jump of H1N1pdm09 to swine in the United States (and worldwide) has led to an increased number of reassortants between various North American swine triple reassortants and H1N1pdm09, and most or all have an H1N1pdm09 M gene.  A recent report noted the increase and gave several examples, most of which were trH1N2 (H1N2v).

However, the first 10 human cases in 2011 were H3N2v as were all reported human cases in the US following the 2009 pandemic.  All of these cases had the same constellation of flu genes (H3N2pdm11), which included one gene (M) from H1N1pdm09.  The two most recent H3N2v cases (trH3N2) match the first ten cases in 2011 in 7/8 gene segments (only the N2 gene is a different lineage).  Thus, all 12 of the 2011 H3N2v cases have an H1N1pdm09 M gene and seven H3N2v genes from North American swine triple reassortants.

The H1N1v described above is the first human cases with H1N1pdm09 (other than the2009 pandemic sub-clade) that is not H3N2v.  However, it is also the first novel isolate with two H1N1pdm09 genes (NA and M).  It also has a gene segment (NP) that matches the 2011 human H3N2v cases.  In addition, the NS gene segment is an H1N2v lineage.

Thus, the human isolate, A/Wisconsin/28/2011 has much in common with the dramatic instability in current swine population, and its frequency in the human population is unclear.  The CDC deposited direct sequences, which were short and only represented four of the eight gene segments, suggesting the RNA levels were low.  Thus, it is unclear if the H1 reacted with the H1N1pdm H1 or NP, and the sample may have been an influenza A unsubtypable, although no such isolate is listed in FluView.

The “Haveyouheard?” announcement does not include key details regarding testing, and the status of linked swine (symptomatic or asymptomatic).  Thus, the likelihood that the case (55M) was infected by the contact swine, or another person is unclear, and more detail would be useful.

However, it is clear that the isolate increases the number of novel serotypes in human in 2011 to three (H1N1v, H1N2v, H3N2v), representing four distinct reassortants, raising concerns that the extreme genetic instability in swine, will be increasingly common in humans.

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