Toronto Adds 2 Sequences to NA Triple Combination Analysis with 286G

Toronto sequences filed at GenBank today add numbers 29 and 30 to ΣPF11 for 286G on Neuraminidase .  The bulk of the PF11 286G sequences cluster in Catalonia, but these two sequences from Toronto augment a NA Triple Combination occurring in Canada.  Canada and Catalonia are the only regions of the world currently reporting this PF11 coding that is also found in 1918 sequences, the high-CFR H5N1 Gharbiyah, Egypt specimens and is common in Seasonal Influenza from 2006, 2007 and 2008.

• A/Toronto/T5294/2009 (TorT5294) collected on 2009-05-30 from 22F
• A/Toronto/C0270/2009 (TorC0270) collected on 2009-05-24 from 33M

These two new Toronto specimens and the other four original Canadian sequences carrying 286G also code for 106V and 248N matching the two TamiFlu resistant sequences from Washington at 106 and 248.

Human-fit Seasonal H1N1 from 2008 and 2009 typically demonstrates the H275Y TamiFlu Resistance marker and a NA Triple Combination at 106, 248 and 286:

106I, 248N, 286G

These two sequences from Toronto in May 2009 follow the worldwide pattern exhibiting a particular permutation of the NA Triple Combination:

106V, 248N, 286G

The two sequences parallel the previously discussed TorontoT5308 sequence with the exception of TorT5294 also showing 382A.

Of the 30 sequences on file bearing 286G, all but Catalonia397 bear 248N and all 30 show 106V.  An intra-segment exclusivity on NA exists presently in PF11 between 106I and 286G though 106I donors are proximal in Catalonia and Canada.

Are we seeing enhanced conservation within a PF11 sub-clade being primed for TamiFlu Resistance?

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