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The New Contagion trH3N2
Recombinomics Commentary 15:30
September 11, 2011

The latest CDC FluView (week35) coincides with the release of the movie “Contagion” and it is worth comparing trH3N2 to the virus in the film, because both are new contagions.  In the movie the agent (MEV) was a recombinant with sequences from bat and swine, and as seen in the samples frozen in liquid nitrogen, the MEV isolates are in the same rack as SARS and H1N1, which is appropriate since SARS is thought to reside in bats, while H1N1 is a triple reassortant of swine origin.

The spread of MEV parallels the SARS CoV, which launched its international spread in Hong Kong.  A physician who had been treating SARS patients in Guangdong Province came to Hong Kong for a wedding.  He stayed at the Metropole Hotel in room 911 and vomited in front of the elevator on the 9th floor.  This led to the infection of vacationers and visitors on the 9th floor ,who then spread the SARS CoV to Hong Kong, Singapore, Hanoi, and Toronto.  There was likely additional spread early, but the above four sites led to a significant number of cases in each location.  SARS CoV had a high case fatality rate, especially in the older patients (40’s to 60’s), but spread was largely limited to the above locations, other than spread in mainland China and Taiwan.

In contrast, H1N1 rapidly spread worldwide and more than 90% of fatalities were in those under 65.  Although the case fatality rate in the younger population is markedly higher than seasonal flu, the overall fatality rate is on a par with seasonal flu because most of those over 65 have immunity due to cross reactivity with the 1918 strain or older seasonal H1N1 sequences.

In Contagion, MEV had a very high case fatality rate (20-25%) and caused a massive number of fatalities (a bit too quickly) in the first month of spread.  Thus, MEV had some aspects in common with SARS (geographic origin and high case fatality rate) and others in common with H1N1 (rapid worldwide spread).  In both real cases the spread was reported promptly and sequences were generated and shared by the scientific community to determine the origin and evolutionary change via phylogenetic analysis, as was also seen in the movie, including a picture of the recombinant 3-D ribbon structure.

However, in addition to jumping from swine to human (as also seen for MEV), H1N1 has also jumped back to swine where there have been worldwide infections leading to additional evolution.  This additional evolution has been seen in the recently released trH3N2 sequences, which have acquired the M gene from H1N1 via reassortment.  This acquisition is in addition to changes acqruired via recombination, which includes the PB1 E618D in early human isolates, as well as several of the recent HA changes, which map to seasonal H3N2.  Thus, trH3N2 is evolving via reassortment and recombination and detection of spread has only recently been released.
Thus, the effects of the H1N1 jump to humans has not been as lethal as MEV in initial cases, but H1N1 continues to spread, even after the development of a vaccine, and the influenza of H1N1 has now been seen in trH3N2 which will likely lead to another pandemic and co-circulation of two pandemic influenza’s leading to more recombination and more problems.
The influence of pandemic H1N1 and trH3N2 is still evolving and the potential for a significant impact remains, even after the development of a vaccine and widespread use of antivirals.
Thus, while H1N1 and H3N2 spread has many parallels with MEV spread and evolution as seen in “Contagion”, H1N1 and H3N2 are still evolving and the spread and effects are and will be quite real.

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