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Commentary

CDC Curious Comments on Novel trH3N2 In US Swine
Recombinomics Commentary 14:20
November 26, 2011

Although reassortment between swine influenza and 2009 influenza A (H1N1) viruses has been reported in pigs in the United States (3), this particular genetic combination of swine influenza virus segments is unique and has not been reported previously in either swine or humans, based on a review of influenza genomic sequences publicly available in GenBank
 
The virus has been isolated from pigs in the U.S. Midwest, says Dr. Nancy Cox, head of the CDC's influenza division, though she won't specify where.

The above comments from the Sept 2 CDC early release MMWR (in blue) followed by a current media report on WHO preparation for a trH3N2 pandemic (in red), describe isolates of the novel trH3N2, first reported in the two cases in the MMWR (A/Indiana/08/2011 and A/Pennsylvania/09/2011) and a CDC claim of sequences in pigs in the US Midwest (which follows the November 22 "Have You Heard?" which falsely claim reported matches in multiple states). 

The comments on the novel trH3N2 in pigs in the US Midwest are curious, because the only public sequence of a swine match is the recently released sequence from New York of a sequence from a sample collected on September 13, A/
swine/NY/A01104005/2011.  The release of  this sequence, in the absence of other swine sequences, strongly suggests it represents the first such example in swine, in spite of increased swine surveillance by USDA and collaborating academic institutions.

These agencies typically release swine sequences at Genbank, which are then added to the sequences at GISAID a few days later.  The above set of sequences, from a Sept 13 isolate, were submitted to Genbank on October 27 and released on November 20, which is a relatively quick release, especially since the submitted sequences were for all eight gene segments, which is also unusual.  Most recent swine and human isolates are represented by sequences from HA, NA, and MP, but this information is sufficient for identification of a “match” with the novel trH3N2 in humans because the 2011 human isolates have a novel combination of HA and NA as well as an MP from H1N1pdm.

The HA and NA sequences were present in 2010 human isolates, but not in the same isolates.  The HA sequence was in the dominant series found in five of the six human isolates from 2010 (A/Minnesota/09/2010, A/Pennsylvania/40/2010, A/Wisconsin/12/20110, A/Minnesota/11/2010, daughter of A/Minnesota/2010 – confirmed serologically).  The NA was present in the other 2010 human isolate, A/Pennsylvania/14/2010.  None of the 2010 human isolates had any gene segments from H1N1pdm09, while all of the human 2011 sequences had the HA and NA combination as well as MP from H1N1pdm09.

Two large sets of sequences from swine were released after the Sept 2 MMWR, and these releases contained isolates that match two of the three genes above, but none matched all three.  One series had the HA and NA combination, but had a trH3N2 swine MP.  Another series had the NA gene with an H1N1pdm09 M gene, but these isolates were H1N2, so there was no H3 match.  A third series was from trH3N2 sequences with an H1N1pdm09 MP gene, but the H3 and N2 were from very distinct lineages.  Although most of the sequences did not included additional gene segments, it is likely that all or most had multiple gene segments from H1N1pdm09 based on a smaller number of sequences representing all eight gene segments from similar isolates.

Thus, prior to the release of the New York sequence, a large number of 2010 and 2011 swine sequences had been released, but as noted in the Sept 2 MMWR, none were matches and the two examples cited in the MMWR of incomplete sequences with an H1N1pdm MP were likely among the two large series of swine sequences released from the USDA swine surveillance program.

Therefore, it is likely that the New York sequence was the first example, and any sequences from US Midwestern swine would be from later collections, which would be expected because after spread of the novel trH3N2 in humans there would be many examples of jumps from humans to swine, as was seen for H1N1pdm09, which was not identified in any swine isolates from samples collected prior to the series of human cases in April 2009, but such isolates have since been found in swine worldwide.

Thus, the detection of the novel trH3N2 in all ten 2011 human isolates, and the detection of the novel virus in just one swine isolate from a sample collected after the spread in humans was expected, but information on the Midwestern states with similar sequences, including the collection dates, would be useful (Recombinomics did contact the USDA shortly after the release of the New York sequence and although the initial written response was prompt and included an intention of providing more detail, such detail has not been received prior to this commentary).

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