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Paradigm Shift Intervention Monitoring
New Human Contagion trH3N2
The acquisition of the M gene likely occurred as a result of swine being co–infected with the swine influenza A (H3N2) virus and the human 2009 H1N1 virus. While we know the M gene plays a role in influenza virus infection, assembly and replication, the significance of this change in these swine–origin influenza A (H3N2) viruses is unknown at this time. CDC continues to investigate the implications of this genetic change.
The above comments from the latest CDC “Have You Heard?” acknowledges the fifth trH3N2 human isolate with the M gene from H1N1pdm09 (pandemic H1N1), as well as an interest in this acquisition, but still maintains the CDC narrative that these infections are rare and linked to close contact in swine, which is not supported by the sequences. The Maine case provided compelling evidence for an emerging trH3N2 human contagion based on sequence data supporting evolution in humans.
This sub-clade has been reported in all five 2010 human isolates A/Indiana/08/2011, A/Pennsylvania/09/2011, A/Pennsylvania/10/2011, A/Pennsylvania/11/2011, A/Maine/06/2011), in contrast to the human trH3N2 sequences in late 2010, where most of isolates shared most of the gene segments. In 2011 all human isolates share all gene segments which create a novel sub-clade which has never been reported in swine, in spite of increased surveillance for SOIV (swine origin influenza virus) in swine.
Recent reports have highlighted the importance of the M gene. One report looked at gene segments in H1N1pdm09 to determine how the virus jumped from swine to humans, and concluded that the M gene segment was critical. Another report noted the increased reassortment in swine from the US and noted that the M gene from H1N1pdm09 was central to the reassortants, which had various H and N swine triple reassortant combinations surrounding internal genes from H1N1 pnd09, including the M gene segments.
Sequences from the increased swine surveillance describe two July isolates (July 16), A/Texas/A01104003/2011 and A/Texas/A01104004/2011, which have all eight gene segments from H1N1pdm09, which contain S188T, which represents the dominant H1N1 circulating in humans in 2011. The recent collection date signals an active surveillance campaign, which has identified additional constellations with an M gene from H1N1pdm09.
Another July isolate (July 8), A/swine/Illinois/A00907647/2011, has an H1N1pdm09 M gene, as well as an NA gene that is closely related to the human trH3N2 isolates. However, this swine isolate has an H1 and is likely to be similar to other H1N2 isolates collected in 2010 (A/swine/Minnesota/A01047604/2010 and A/swine/South Dakota/4/2010)) and 2011 (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), which have multiple internal genes from H1N1pdm09.
In addition to H1N2 isolates with an H1N1pdm09 M gene, enhanced surveillance has also found H3N2 swine isolates (A/swine/Texas/A01049555/2011, A/swine/Texas/A01049556/2011, A/swine/Indiana/A01049750/2011, A/swine/Texas/A01049914/2011, A/swine/Texas/A01049915/2011) which likely have a similar set of internal genes (only the M gene sequence has been released in addition to the H3 and N2 sequences). However, this swine H3 gene is easily distinguished from the H3 sequence found in all human 2011 trH3N2 isolates, which is closely related to the dominant sequence found in the human 2010 trH3N2.
This sequence has also been found in 2010 and 2011 swine isolates (A/swine/Indiana/A0109091/2010, A/swine/Indiana/A01049744/2011, A/swine/Indiana/A01049745/2011, A/swine/North Carolina/A01049436/2011, A/swine/Indiana/A01049653/2011), but these swine isolates have a swine M gene.
Thus, none of the swine isolates, including those from July, 2011,, match the human 2011 isolates, which match each other in all 8 gene segments.
This human sub-clade has evolved from the 2010 human trH3N2 isolates, which match in 5 of the 8 gene segments (PB2, PA, HA, NP, NS). The PB1 represents the same lineage, but is more closely related to the sequences from 2007 H1N1 isolates, A/Ohio/01/2007 and A/Ohio/02/2007, which did not have E618D, which emerged in human trH3N2 (and is present in virtually all H1N1 pdm09 isolates). The NA is in the above swine H1N2 isolates, but is also in the second 2010 human trH3n2 isolate, A/.Pennsylvania/14/2010, from Pennsylvania. Thus, all eight gene segments in all five human 2011 isolates have been found in prior human isolates, once again signaling human adaptation.
Thus, the presence of these eight gene segments in all five human isolates, and the absence in all reported swine isolates, strongly supports human transmission, and the absence of human isolates without swine contact raises concerns that such isolates have been withheld because the absence of a swine epidemiological link is still under investigation.
Details on such cases should be released immediately.