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Paradigm Shift Intervention Monitoring
Curious Comments On trH3N2 In US Swine
The above comments by the CDC in the December 23 MMWR early release are curious. The sequencing of the 150 SIV isolates by the USDA signals an enhanced surveillance, but it is well known that this surveillance has only produce one isolate, A/swine/NY/A01104005/2011, that matches the first 10 human trH3N2 (now called H3N2v) cases (designated H3N2pdm11). The identification of matches is straight forward.
The first 10 human trH3N2 isolates in 2011 have the same constellation of genes and the same lineage for each of the eight gene segments. Five of the eight genes (PB1, PA, HA, NP, NS) match the dominant sequences from the 2010 human cases (represented by A/Pennsylvania/40/2010 and A/Wisconsin/12/2010). The other three gene segments (PB1, NA, MP) are present in a recently released trH1N2 isolate, A/swine/Ohio/FAH10-1/2010, which includes the H1N1pdm09 M gene). Thus, the 2011 human isolates have an H3 that is matched in the first ten 2011 isolates (as well as the two H3N2v isolates from West Virginia), and 5 of the 6 human isolates from 2010 (as seen in the CDC HA phylogenetic tree, slide 6, which includes the 2010 human isolates), as well as the H1N1pdm09 M gene, as seen in the recent H1N2 parental sequence from Ohio.
That analysis quickly eliminates all of the USDA sequences except for the known match from New York. This sequence was recently released by the USDA, and in contrast to the earlier isolates, it was released alone (instead of in a large batch of swine sequences), and sequences for all eight gene segments were released. Thus, in addition to an HA match in an H3N2 swine isolate with a H1N1pdm09 M gene, the other six gene segments also matched.
In contrast the other H3N2 swine isolates have an HA sequence that is easily distinguished from the 10 human and one swine sequences above. Two of the non-matches are 2010 isolates from Iowa, and the USDA has released sequences for the other 5 gene segments showing multiple mismatches for the H3nN swine lineages.
The 2011 USDA H3N2 swine sequences with a mis-matched HA are similar to full sequences from Kansas isolates. The Kansas isolates have multiple internal genes which match H1N1pdm09, in contrast to the human cases which have only one gene segments (M) that match H1N1pdm09.
Thus, it is unclear why the CDC fails to note that there is only one swine match in the USDA or any sequence at Genbank. Other than the New York match, all Genbank USDA swine sequences were deposited October 1, 2011 or earlier. An earlier media report quoted Nancy Cox from the CDC to indicate a match from the Midwest had been identified, but this sequence has not been made public, and therefore the collection date is unknown.
The public sequence is from a Sept 13 isolate, indicating a failure to identify a match in the 150 sequences from isolates collected prior to the human Indiana and Pennsylvania sequences from July and August collections. The USDA series has a few isolates from July, but most of the 2011 sequences are from collections during the first six months. The USDA will undoubtedly release more swine sequences from isolates collected at later dates, and eventually more matches will be identified.
However, the current sequences indicates swine matches are rare, and have yet to be identified in any isolate collected prior to the 2011 human cases.
Moreover, the two most recent human H3N2v isolates, A/West Virginia/06/2011 and A/West Virginia/07/2011 match the H3N2pdm11 in 7 of the 8 gene segments (the N2 is from swine H3N2), so none of the published swine sequences match these two human isolates.
Thus, it is unclear why the CDC failed to note the lack of matches in the 150 public sequences generated by the USDA, and why they include the misleading comments in the December 23 early release MMWR on H3N2v cases and sequences.