Novel Human trH3N2 Constellation Raises Concerns
Recombinomics Commentary 14:40
November 17, 2010

Dates of illness onset in the two patients are more than six weeks apart and the viruses from the two patients have some genetic differences, confirming that these two cases are not linked.

The viruses identified in Pennsylvania and Wisconsin are similar to viruses that infected a patient in Iowa in September 2009, a patient in Kansas in August 2009 and a patient in Minnesota in May 2010.

The above comments are from the CDC’s week 44 FluView report as well as an update on triple reassortant H3N2 (trH3N2).  Unfortunately, the statements lack scientific precision and the sequences from the cases have been withheld.  The CDC did release one set of sequences, A/Kansas/13/2009 (KS/13), from the August 2009 outbreak, but no other sequences have been released.  Sequences from each of the above cases would allow for phylogenetic analysis which would identify the precise relationship between the sequences.  Although all are clearly trH3N2 cases, sequences would provide relationships between the sequences including changes due to reassortment and/or recombination.

Such analysis of the released set of sequences demonstrates that the isolate was formed from at least three sets of parental sequences.  trH3N2 sequences in general have three gene segments from human flu (PB1, HA, NA), two from avian (PB2 and PA), and three from swine (NP, MP, NS).  However, human and swine H1 and N1 circulate in swine, so swapping of H and N genes can create H1N1 and H1N2 reassortants, including pandemic H1N1, which has swine H1 and N1.  However, the genes evolve independently, allowing for further phylogenetic analysis.  The internal genes from trH3N2 isolates are distinct from the internal genes from pH1N1 (although the origins are similar with human PB1 and avian PA and PB2).

Further phylogenetic analysis using swine trH3N2, trH1N1, and trH1N2 indicate KS/13 has a novel constellation of gene segments. The HA and NA genes are related to other trH3N2 swine sequences found in the same areas as the human trH3N2 cases.  One of the internal genes, NP, is related to another series of swine trH1N1 and trH1N2 sequences from NC, MN, MO, NE (see list here).  However, five of the six internal gene segments were closely related to the human and swine trH1N1 sequences isolates from the 2007 Huron County fair in Ohio.  Sequences from presenters were generated and about 2 dozen fair attendees had flu-like symptoms, which is uncommon for Ohio residents in August.  Thus, it is likely that the trH1N1 in swine at the fair had significant spread to humans. 

Thus, KS/13 has a novel constellation of trH1 and trH3 gene segments, which would be present in other cases if KS/13-like influenza was spreading in the human population.

Therefore, full sets of trH3N2 cases should be released immediately.

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