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Dynamic H3N2v Human Adaptation
Recombinomics Commentary 23:45
April 25, 2012

The child had contact a week prior with swine at a family-owned slaughterhouse.

Contact with swine in the week preceding onset of the child’s illness was reported.

The above comments are from an April 9 post by the Canyon View Medical Group, with offices in Weber County, Utah (in blue), and April 13 FluView comments by the CDC (in red).  The Canyon View post was two days prior to the press release by the Weber Morgan Health Department and 3 days prior to the initial announcement by the CDC suggesting the Canyon View Medical Group had first-hand knowledge of this case.

Although the descriptions of the date of swine contact are not mutually exclusive, contact 7 days prior to disease onset, would diminish the relevance of the swine exposure, since swine flu, like seasonal flu has a typical incubation period of 1-2 days.  Moreover, the USDA has also stated that it had no indication of ill swine at the processing plant.

However, sequence analysis provides compelling evidence for an H3N2v evolving toward human spread via adaptations which appear in human isolates prior to detection in swine isolates.  This type of evolution for H3N2v is similar to analysis of H1N1pdm09, which was first identified in humans, followed by jumps back into swine, which has now been detected worldwide.

Although H1N1pdm09 is a triple reassortant, it is easily distinguished from the triple reassortants in swine in the United States or the 13 human cases identified prior to the 2009 H1N1pdm09 pandemic.  Increased surveillance failed to identify H1N1 in any samples collected prior to the start of the pandemic, but humans spread H1N1pdm09 worldwide, and it has been found in swine in every continent except Antarctica.

In addition to have two gene segments which are typically found in Europe, the “North American” segments also represent lineages distinct from those in swine in North America.  One polymorphism that is in H1N1pdm09 but not lineages in North America is PB1 E618D, which appeared in the first human H3N2v in the United States, A/Kansas/13/2009.  This marker was subsequently found in all 6 H3N2 human cases in 2010, and did not appear in any swine isolates until the fall of 2010.

The PB1 in the human cases, as well as the other internal genes were related to two (A/Ohio/01/2007 and A/Ohio/02/2007) of the 12 H1N1 cases identified prior to the H1N1pdm09 pandemic.  Both were from the Hudson County fair, which was the only venue with two confirmed cases.  Moreover, 28 attendees had influenza-like illness, indicating these internal genes were adapting to human transmission.

Clustering of H3N2v human cases in 2010 involved these genes, and most of the human isolates had most of these genes.

However, in 2011 a new reassortant emerged which had acquired three gene segments from H1n2, similar to an isolate for Ohio, .  Once again this novel constellation appeared in human cases in Indiana (A/Indiana/08/2011) and Pennsylvania (A/Pennsylvania/09/2011,  A/Pennsylvania/10/2011, A/Pennsylvania/11/2011) prior to detection in swine (A/New York and A/Iowa).

In contrast to the six human isolates in 2010, the first 10 human isolates in 2011 matched in all eight genes, once again signaling human adaptation.

In late 2011 and novel constellation appeared, which had acquired N2 from another swine lineage.  Both West Virginia isolates (A/West Virginia/06/2011 and A/West Virginia/07/2011) were from a Mineral county day care center and were epidemiologically linked as were 22 additional cases with influenza-like illness.  This large cluster led to another alert by the CDC, yet no cases were identified during the peak of the flu season.  The first case in 2012 was from Utah (A/Utah/10/2012) and was virtually identical to the sequences from West Virginia, signaling further adaptation.  Once again, the evolving H3N2v was found in humans prior to swine.  This constellation has not been reported in swine, including cases from later 2011 and early 2012.

Thus, the USDA has an aggressive swine surveillance program, which has identified hundreds of cases since the 2009 H1N1pdm09 pandemic, yet H3N2v evolution associated with human adaptation are found in human cases prior to swine, and these adapted sequence are found in human clusters of cases with no swine exposure.  Although the latest case does have an exposure 7 days prior to symptoms, this exposure leads to more aggressive testing, creating a pseudo-linkage, which is once again becoming a CDC focus.  In a recent podcast, CDC researchers are once again requesting samples from cases linked to asymptomatic swine, instead of aggressive testing of young children with influenza like illness.

The end of the current flu season should lead to record numbers of H3N2 human cases.

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