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trH3N2 M Gene Acquistions Raise Pandemic Concerns
Recombinomics Commentary 19:11
September 19, 2011

Of 99 event pig-exposed students, 72 (73%) participated in the investigation, and 42 (42%) provided serum samples, of whom 17 (40%) were seropositive

The above comments are from a recent paper highlighting the efficient transmission of trH1N1 from swine to students at a livestock even in late 2008 in South Dakota.  A full set of sequences, A/South Dakota/03/2008, from the index case (19M) have been made public, and these sequences highlight the role of the M gene in transmission.

trH3N2 cases in 2010 led to a pager alert issued by WHO involving two patients from who full sequences were released (A/Wisconsin/12/2010 and A/Pennsylvania/14/2010).  Although these isolates could be distinguished (in HA and NA) the M gene in both cases were closely related to each other as well as the South Dakota isolate above.  Moreover, two subsequent sets of sequences (A/Pennsylvania/40/2010 and A/Minnesota/11/2010) also had a M gene that matched (see list here).

Three of the 2010 trH3N2 isolates were closely related to each in the HA and NA genes, again indicating these human isolates were dominant in late 2010.  Moreover, the other internal genes were closely related to sequences from an outbreak at the Huron County fair in 2007, where trH1N1 was isolated (A/Ohio/02/2007 and A/Ohio/01/2007) from a presenter (10F) and her father (36M), respectively, and two dozen fair attendees had flu-like symptoms. Thus, the human isolates in 2010 had acquired genes from isolates that had been linked to efficient transmission to humans.

The role of the M gene in efficient transmission to humans was highlighted in another paper which generated various reassortanst using genes from the H1N1 pandemic virus and concluded that the M gene was critical for efficient transmission to humans (as determined in a guinea pig model).

The recent isolates from Indiana (A/Indiana/08/2011) and Washington County in Pennsylvania (A/Pennsylvania/09/2011, A/Pennsylvania/10/2011, A/Pennsylvania/11/2011) all have the same constellation of genes with five matching the three closely related sequences from 2010, an NA matching the other isolate from 2010 (PA/14/10), and a M gene segment from pandemic H1N1.

The efficient transmission of trH1N1 in South Dakota and Ohio indicate human infections by swine are not rare.  The recent human cases demonstrate a clustering of gene segments which link back to the high transmission events, and the acquisition of pandemic H1N1 suggests that the number of trH3N2 cases is orders of magnitude higher than the four recently confirmed cases.

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