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PB1 E618D In Novel trH1N2 Minnesota Case Raises Concerns
Recombinomics Commentary 12:20
December 11, 2011

The Minnesota case, with the unrelated virus, is still under investigation, Finelli said. The child had no contact with pigs, but may have been in contact with a sick child a day or two before becoming ill.

The above comments from the Helen Branswell piece on the latest novel US cases, including the trH1N2 Minnesota case, A/Minnesota/19/2011 (MN/19/11), suggest that the novel influenza is transmitting in humans.  However, this is not unrelated to H3N2pdm11.  Like H3N2pdm11, the novel trH1N2 is a reassortant between the same parents, the dominant 2010 human trH3N2 sequences and an H1N2 with human genes which trace back to seasonal H1 and N2 from 2003.

Prior to the 2009 trH1N1 pandemic, there were no reported human trH3N2 cases in the United States.  The first case, A/Kansas/13/2009, acquired PB1 E618D, which was in virtually all H1N1pdm09 sequences, via recombination.  This acquisition was also in all six of the human 2010 isolates (A/Minnesota/09/2010, A/Pennsylvania/40/2010, A/Wisconsin/12/2010, A/Pennsylvania/14/2010, A/Minnesota/11/2010, and the daughter of A/Minnesota/11/2010, who had no swine contact).

Prior to the detection of the Kansas trH3N2, E618D was not found in any swine isolates, other than H1N1pdm09 infections.  The first examples were in the Pennsylvania trH3N2 swine, (A/swine/Pennsylvania/62170-1/2010, A/swine/Pennsylvania/62170-2/2010, A/swine/Pennsylvania/62170-3/2010, A/swine/Pennsylvania/62170-4/2010) which were related to A/Pennsylvania/14/2010 (PA/14/10), who had no swine contact. This absence of swine contact suggests PA/14/10 was circulating in humans, who may have infected the swine, which is supported by phylogenetic analysis which indicated the swine sequences evolved from PA/14/10. E618D was also subsequently found in an Pennsylvania swine, A/swine/Pennsylvania/057108-1/2010. Similarly, E618D was found in a Minnesota H1N1 swine isolate, A/swine/Minnesota/A01047613/2010, which evolved from A/Minnesota/11/2010, again suggesting that the appearance of E618D in swine isolates, other than those infected with H1N1pdm09, were due to infections of swine by humans carrying one of the 2010 trH3N2 isolates identified in late 2010.

The formation of human trH3N2 led to the acquisition of PB1, NA, and MP from A/swine/Ohio/FAH10-1/2010, which swapped out PB1 with a H1N1pdm09 origin E618D, while acquiring an M gene originating from H1N1pdm09.

The formation of trH1N2 in 2011 involved the same parent lineages, but the trH1N2 provided the H1 and N2 on a human trH3N2 genetic background.  Thus, the 2010 trH3N2 PB1 was retained, which had E618D.  Moreover, the NA matched the lineage in H3N2pdm11, because of a common acquisition.  MN/19/.11 has an NA which is closely related to the first H3N2pdm11 isolated from Pennsylvania, A/Pennsylvania/09/2010 (PA/09/10).  Moreover, two other genes, which are closely related in 2010 trH3N2 and 2011 H3N2pdm11 isolates, NP and NS. are closely related in PA/09/10 and MN/19/11.

Thus, although MN/10/11 has a different serotype, all six internal genes match the lineage of human 2010 trH3N2, and the N2 matches H3N2pdm11.

The frequent reassortment seen in swine after H1N1pdm09 spread throughout swine herds worldwide has raised concerns the rapidly evolving genome will also apread in other species, including humans.  In addition to MN/19/10, the CDC released sequences for a novel H3N2pdm11, A/West Virginia/06/2011, which had acquired a N2 which also traces back to seasonal N2 from 2003, but is a different lineage, signaling more reassortment. 

Therefore, all human cases in 2010 and 2011 have H1N1pdm09 linked changes, either PB1 E618D or the M gene, raising concerns that these new reassortants will spread in humans.  All of these isolates have an N2 tracing back to seasonal H3N2 or seasonal H1N2 from 2003, and an H1 or H3 also tracing back to seasonal H3N2 or H1N1, which may target children., due to a lack of prior exposure to these lineages

However, enhanced surveillance has focused in the Iowa neighborhood of the daycare center linked to the Iowa cluster, as well as patienst with a history of swine exposure, and has yet to focus on children throughout the United States who do not have a swine exposure.

Enhanced surveillance in this vulnerable population is long overdue, and the recent trH1N2, trH3N2, and H3N2pdm11 cases in children, coupled with abysmal surveillance,
continue to increase pandemic concerns.

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