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Commentary
Evolution of
New Human Contagion trH3N2
Recombinomics Commentary 19:40
October 4, 2011
The 2011 trH3N2 human sequences extended the spread of the 2010 human trH3N2 sequences by retaining 5 of the 8 gene segments. The new contagion has swapped out the other three gene segments, PB1, NA, MP for genes found in earlier human triple reassortants (trH1N1, trH3N2, pandemic H1N1), to create a new human contagion, trH3N2, that can efficiently transmit in humans. As has been mentioned by the CDC and WHO, the 2011 human trH3N2 sequences have acquired a pandemic H1N1 M gene segment, which is critical for the efficient transmission of pandemic H1N1 between humans.
However, the human trH3N2 sequences have also acquired the N2 that was in one of the 2010 Pennsylvania cases, A/Pennsylvania/14/2010, as well as a PB1 more closely related to sequences from the Huron County fair (A/Ohio/01/2007 and A/Ohio/02/2007) and this new constellation of genes was in all four 2011 human trH3N2 cases reported to date, and not in any of the reported swine sequences, including the recently released sequences (trH3N2 and trH1N2) from 2010 and 2011.
The recently released 2011 swine sequences had information on HA, NA, and MP, but this limited sub-set failed to match the human trH3N2 constellation. In 2010 there were H1N2 sequences (including A/swine/Minnesota/A01047604/2010 and A/swine/South Dakota/4/2010) with a pandemic H1N1 M gene and an N2 that matched the recent human trH3N2 sequences. However, a more complete analysis of the Minnesota sequence showed that all six internal genes matched pandemic H1N1, and other such sequences (all six pandemic H1N1 internal genes wrapped in H and N from other triple reassortants) have been widely reported in swine, but not in humans. Therefore, it is likely that the recent H1N2 swine sequences (including A/swine/Illinois/A00907647/2011 collected July 8, 2001 as well as additional 2011 isolates such as A/swine/Minnesota/A01049956/2011, A/swine/Iowa/A01049723/2011, A/swine/Iowa/A01049728/2011, A/swine/Indiana/A01049964/2011, A/swine/Illinois/A01049871/2011, A/swine/Illinois/A01049872/2011, A/swine/Iowa/A01049887/2011, A/swine/Iowa/A01049722/2011) have a similar constellation (as well as a different serotype).
Other recent trH3N2 isolates (including A/swine/Texas/A01049555/2011, A/swine/Texas/A01049556/2011, A/swine/Iowa/A01049750/2011, A/swine/Texas/A01049914/2011, A/swine/Texas/A01049915/2011) have a pandemic M gene segment, but different H3 and N2. Similarly, recent isolates have a matching H3 and N2 (including A/swine/Indiana/A01049744/2011, A/swine/Indiana/A01049745/2011, A/swine/North Carolina/A01049436/2011, A/swine/Indiana/A01049653/2011, A/swine/Indiana/A0109091/2010) but have an M gene related to the 2010 trH3N2 isolates.
Thus, even though the surveillance of 2010 and 2011 swine has increased (including one sequence from July, 2011), none of the public sequences match the 2011 human trH3N2 constellation, strongly suggesting that this new pathogen is transmitting in humans.
The number of human cases has been limited, but all four 2011 isolates have the same constellation of genes including a pandemic H1N1 M gene, which is critical for human to human transmission. Moreover, three of the four sequences are virtually identical, but isolated from distinct locations, including the Indiana case with no swine contact. Moreover, none of the four cases were epidemiologically linked, indicating each infection was independent.
The matching of all four human cases, in the absence of any matches with swine isolates signals an adaptation and spread of this trH3N2 contagion with a novel constellation of flu genes.
The limited testing of H3N2 cases, and the focus on patients with links to swine, continues to raise pandemic concerns.
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