TamiFlu Resistance #10 on Novel PF11 Sub-Clade, A/Tokushima/2

The tenth TamiFlu Resistant specimen with a publicly available sequence, A/Tokushima/2, from 2009-07-18 was deposited today at GenBank with only Segment 4 (HA) and Segment 6 (NA).

The NA of Tokushima2 is an exact match (469/469) with Denmark528, HK2369, Yamaguchi22, Hunan SWL3 and Singapore57.  Zoonosis is always at work during an Influenza Flux and this time we seem to be reverting.  A careful look at this Tokushima2 sequence at the nucleotide level appears to demonstrate the emergence of a novel sub-clade within ΣPF11 due to the SNP C435T coding for a synonymous Serine at residue 145 (145S).

This synonymous genetic acquisition does not appear to be found on any available PF11 background at this time, but does appear widely in swine and avian H1N1 across Thailand and Europe including Italy, Spain, the UK, Scotland, Denmark, Belgium, Germany and France between 1980 and 2007.  More strikingly, the SNP appears recently in a 2005 Korean avian H3N8, a 2005 Italian avian H5N1 and a 2006 Italian swine H3N1.  Previous specimens demonstrate that C435T seems to cross serotypes easily, appearing on H4N1, H6N1 and H10N1.

On Tokushima2 TamiFlu Resistance is indicated in typical PF11 fashion via a Single Nucleotide Polymorphism coding for 275Y on the Neuraminidase. The sequence displays the following NA Quadruple Combination:

106I, 248D, 275Y, 286S

The following permutations are now represented on the ten PF11 anti-viral resistant sequences:

106V, 248N, 275Y, 286S = WA28, WA29, TX47
106I, 248N, 275Y, 286S = Osaka180
106I, 248D, 275Y, 286S = HK2369, Yamaguchi22, Denmark528, Hunan SWL3, Singapore57, Tokushima2

Until the 2009-08-21 deposit of the two Washington sequences, all 275Y TamiFlu-Resistant specimens on PF11 backgrounds were paired with 106I. Today we see 3 of 10 with 106V.

The addition of Tokushima2 continues to leverage position 248 toward Aspartate (D) with 6 specimens versus 4 with Asparagine (N). No TamiFlu Resistant specimen on file displays 286G as yet.

The Tokushima2 HA also carries a synonymous SNP coding for 277N that is only found in two sequences within ΣPF11, A/Castro/JXP and A/Stockholm/28.

A more robust database of sequences would be useful.

An n higher than 10 gives us a place to begin.

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