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trH3N2 Sequence Cluster Raises Pandemic Concerns
Recombinomics Commentary 14:20
August 29, 2011

The recently released Indiana trH3N2 HA sequence, A/Indiana/08/2011, is closely related to multiple 2010 human trH3N2isolates (A/Wisconsin/12/2010, A/Pennsylvania/40/2010, A/Minnesota/11/2010), and the collection date of July 24, 2011 suggests it may the  trH3N2 case cited in the week 30 MMWR on August 5, 2011.  The CDC has not updated its website on recent human cases involving trH3N2, and has not provided any detail on this case (1M), other than collection date, age, and gender on the sequence characterization sheet..

However, the close relationship to the earlier isolates above raises concerns that this H3 sequence is transmitting in humans.  The above Wisconsin and Pennsylvania cases were symptomatic within a week of each other (September, 2010), raising concerns that a sub-clade with this H3 sequence was transmitting among humans last fall.  This concern was increased by the H3 sequence of the Minnesota isolate (November, 2011), which was virtually identical to the two earlier isolates.  The concern was increased further by the report indicating the daughter of the Minnesota case (31M) was also serlogically confirmed to have been trH3N2 infected (without swine contact), and additional contacts had ILI  (influenza like illness).

The recent selection of the sequences of the index case as a potential trH3N2 vaccine target added to these concerns.  All of the earlier cases were due to infections in late 2010.  The Indiana sequence demonstrates the continued circulation of this H3 sequence in humans.  The H3 sequence has a cluster of six consecutive polymorphisms (G855A, C866A, G872A, C873T, A874A, and C876A) which are present in all four human sequences, as well as two recent swine sequences (A/swine/North Carolina/A01049436/2011 and A/swine/Indiana/A0109091/2010) generated by the Veterinary Diagnostic and Production Animal Medicine at Iowa State University.  This department and the USDA at ISU have markedly increased the number of recent swine H3 sequences, and the latest sequences demonstrate the preferential clustering of this H3 related sequence in human isolates. 

This clustering increases concerns regarding human transmission.  The latest human isolate from Indiana is a reassortant.  Although the H3 and N2 sequences are closely related to the swine sequences, the MP sequence matches the pandemic H1N1 sub-clade, signaling an independent introduction of this isolate into the human population.  The Indiana isolate is the first example of a human trH3N2 with a pandemic H1N1 gene.

However, although this isolate represents a new introduction, the close H3 match with the three earlier sequences (and trH3N2 linked to the MN cluster), indicates this H3 is linked to more efficient transmission of trH3N2 in humans.

More information on the Indiana case and symptomatic contacts would be useful.

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