Rhiza Labs FluTracker Forum

The two recent novel trH1N2 and trH3N2 cases highlight the level of reassortment among the recent novel human isolates. This instabilty in human cases creates significant problems for vaccine targeting, and raises serious pandemic concerns.

The various combinations and concerns will be delineated on this thread.

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PB2 2010 sequences form two major branches, with MN/09/10, PA/40/10, WI/12/10, and MN/11/2010 on one branch, and PA/14/10 (as well as PA swine) on another branch.

The PA/14/10 branch then gives rise to ME/06/11 (and presumably ME/07/11), MN/19/11, and WV06/11.

A well formed separate branch then forms two branches with IN/08/11 and PA/09/11 (and presumably PA/10/11 and PA/11/11) on one branch, and IN/10/11, sw/NY/11, IA/07, IA/08, IA/09 on the other branch.

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PB1 forms two distinct branches. One branch has the 2010 trH3N2 sequences (MN/11/10, PA/14/10, PA/40/10, WI/12/10, PA swine) and MN/19/11.

The other branch has OH swine followed by two branches with IN/10/11, PA/09/11 (and presumably PA/10/11, PA/11/11), IN/08/11 on one branch; and sw/NY/11, ME/06/11 (and presumably ME/07/11), WV/06/11, and IA/07/11, IA/08/11, IA/09/11 on the other branch.

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The PA sequences all (except MN/11/10) fall on a well defined branch. Closely related sequence form two branches. One has WI/12/10 and MN/19/11 while the other has PA/14/10, PA swine, and presumably PA/40/10. That leads to two more closely related branches with PA/11/11 (and presumably PA/09/11 and PA/10/11) and identical IN/08/11, along with sw/NY/11 on one branch, with ME/06/11 and presumably ME07/11 on the other. That is followed by another branch with IN/10/11 and WV/06/11 with a more evolved IA/07/11, IA/08/11, IA/09/11.

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PB1 E618D

EPI346499 A/Minnesota/19/2011 (A/H1N2) segment 2 (PB1) 38.1 3.399117e-03 20/20 (100%)
EPI314789 A/swine/Minnesota/A01047613/2010 (A/H1N1) segment 2 (PB1) 38.1 3.399117e-03 20/20 (100%)
EPI312979 A/Pennsylvania/40/2010 (A/H3N2) segment 2 (PB1) 38.1 3.399117e-03 20/20 (100%)
EPI307927 A/swine/Pennsylvania/057108-1/2010 (A/H3N2) segment 2 (PB1) 38.1 3.399117e-03 20/20 (100%)
EPI302685 A/swine/Pennsylvania/62170-4/2010 (A/H3N2) segment 2 (PB1) 38.1 3.399117e-03 20/20 (100%)
EPI302680 A/swine/Pennsylvania/62170-3/2010 (A/H3N2) segment 2 (PB1) 38.1 3.399117e-03 20/20 (100%)
EPI302673 A/swine/Pennsylvania/62170-2/2010 (A/H3N2) segment 2 (PB1) 38.1 3.399117e-03 20/20 (100%)
EPI302668 A/swine/Pennsylvania/62170-1/2010 (A/H3N2) segment 2 (PB1) 38.1 3.399117e-03 20/20 (100%)
EPI293963 A/Minnesota/11/2010 (A/H3N2) segment 2 (PB1) 38.1 3.399117e-03 20/20 (100%)
EPI291895 A/Wisconsin/12/2010 (A/H3N2) segment 2 (PB1) 38.1 3.399117e-03 20/20 (100%)
EPI291867 A/Pennsylvania/14/2010 (A/H3N2) segment 2 (PB1) 38.1 3.399117e-03 20/20 (100%)
EPI291840 A/Minnesota/09/2010 (A/H3N2) segment 2 (PB1) 38.1 3.399117e-03 20/20 (100%)
EPI244299 A/Kansas/13/2009 (A/H3N2) segment 2 (PB1) 38.1 3.399117e-03 20/20 (100%)

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The above list demonstrates PB1 E618D in all human trH3N2 prior to H3N2pdm11 emergence in 2011 (except IA/16/09). PB1 E618D was in virtually all H1N1pdm09 isolates. In 2011 the human cases swammped out the PB1 with E618D for the PB1 in Ohio parent, but acquired H1N1pdm09 M gene. Thus, virtually all human cases have a H1N1pdm09 acquisitions - PB1 E618 via recombination, or H1N1pdm09 M gene via reassortment.

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It is also worth noting that phylogenetic analysis indicates the swine isolates with E618D evolved from the human cases.
The Pennsylvania swine evolved from A/Pennsylvania/14/2010, while the Minnesota swine evolved from A/Minnesota/11/2010, which is also seen in the NP tree (and MN11 is a PA outlier, but it matches the above sw/MN/10, which was isolated in Dec, 2010, AFTER the MN cluster).

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NP sequences all closely related and on same branch. At the base is IN/10/11, ME/06/11 (and presumably ME/07/11), PA/40/10. Closely related branch has MN/11/10 with evolving sw/MN/10. Another well defined branch has PA/09/11 leading to MN/19/11. Another branch has WI/12/10 leading to PA/14/10 leading to PA swine. Largest branch is split into two branches, with sw/NY/11 and PA/11/11 and presumably PA/10/11 and IN/08/11 on one branch, and WV/06/11, IA/07/11, IA/08/11, IA/09/11 on the other branch.

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NS sequences are also closely related. The base of the branch has PA/40/10, PA/09/11, WI/12/10, MN/11/10, sw/MN/10, MN/19. One branch off the base jas PA/14/10 and PA swine. Another barnch has two arms. One has IA/07/11, IA/08/11, IA/09/11 and the other has IN/10/11. Another branch off the base has IN/08/11 leading to PA/10/10 and PA/11/10. Another branch off the basse has sw/NY/11 and WV/06/11 leading to ME/06/11 (and presumably ME/07/11).

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The MP sequences for the isolates with trH3N2 swine MP form a well defined branch with PA/14/10 and PA swine on one arm, WI/12/10, MN/11/10, PA/40/10 on another arm, and MN/19/11 formimg a third arm.

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