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The Emerging H3N2 Swine Pandemic
Recombinomics Commentary 23:10
December 17, 2010

This case of human infection with swine origin influenza virus (SOIV) brings the total number of human infections with swine origin influenza viruses reported to CDC since 2005 to 19. Previously, five of these reports had been swine origin A (H3N2) viruses. The most recent Minnesota case brings the number of reports swine origin A (H3N2) infections in humans in the United States to six. Human infections with swine origin H3N2 virus infections have also been reported from Pennsylvania and Wisconsin in October and November 2010, Minnesota in May 2010, Iowa in September 2009, and Kansas in August 2009.

The above comments are from the latest CDC update on H3N2 triple reassortants (trH3N2).  As noted above, there have been 19 reported cases involving triple reassortants, but the six most recent cases have all been trH3N2.  Moreover, the sequences from the five isolates collected prior to the current case raise concerns that these cases are due to human to human transmission, especially for four of the five released sequences.  These four sequences include the first case (Kansas/13/2009 in August 2009) as well as the three most recent sequences (Minnesota/09/2010 in May 2010, Pennsylvania/14/2010 in October 2010, and Wisconsin/12/2010 in November 2010).  These four cases share multiple polymorphisms in multiple genes which are not found in any recent swine sequences, even though swine surveillance has increased because of the 2009 pandemic.

Thus, the four human sequences are more closely related to each other than any public swine sequences.  One marker, PB1 E618D, is found in almost all pandemic H1N1 sequences, but not in any recent swine sequences.  Its presence in the four human trH3N2 sequences may signal human adaptation and human to human transmission.  Although there have been many trH1N1, trH1N2, and trH3N2 swine sequences generated in the past few years, including sequences from 2009 and 2010, the human trH3N2 sequences have polymorphism present in all four human isolates, but no recent swine sequences.  Similarly, although the CDC updates cites swine contacts for most cases, they have not indicated any trH3N2 virus has been detected in the contact swine and there are no public sequences that would be candidates for the swine source of the human infections.

The timing and location of the most recent case from Minnesota suggest that sequences will be very closely related to these four isolates, which would add additional data supporting human to human transmission.

Detection of the human cases is difficult because the H3 and N2 have a human origin.  Thus, the triple reassortant identity can be determined by antigenic characterization assays, where the trH3N2 sequences would be “low reactors” or by sequencing, which would readily show the close identity with the prior trH3N2 sequences, including a swine origin for three (NP, MP, NS) of the eight gene segments as well as an avian origin for two (PB2 and PA) of the eight segments.

It is unclear why the number of trH3N2 examples has been limited to the six most recent TR isolates.  However, the announcement for the three most recent cases has been delayed, so the number of cases under investigation or analysis may be higher than the recent three cases.  The relatedness between human isolates supports human to human transmission and an emerging swine H3N2 pandemic.

Release of sequences from the most recent case, and information about additional cases and recent samples would be useful.
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