TamiFlu Resistance #12 from Canada, A/Quebec/147365, may drive Unique HA Polymorphism

The twelfth TamiFlu Resistant specimen with a publicly available sequence, A/Quebec/147365, was deposited today at GenBank with all 8 segments.  We shall examine the primary antigens today, Segment 4 (HA) and Segment 6 (NA).

The antigen Hemagglutinin is of interest on this specimen due to the 259S introduction into ΣPF11. Antigens expressing novelty in areas that may affect Human Receptor Binding bear scrutiny.  A second Quebec specimen today is an exact nucleotide match to the HA, A/Quebec/147023 HA.  More important than the novelty and the prospect that the 259S change has spread is the fact that 98 other sequences in the reservoir are a 1700/1701 nucleotide match (99+%) with these two, offering a wide geography for future recombination:


Sequence Count

New York


US (other)














Europe (other)


South America


You will recall that we've observed significant movement in the domain surrounding residue 259, including the boarding school cases with 259V in Jiangyin, 261V in Singapore, 263D in Tomsk, 264X in Jiangyin, 264S in TamiFlu Resistant WA29 and 264T in NY and Spain. 

259S appears to be found only on Swine H1 from 2003 in two North Carolina samples (NCsw35279, NCsw36681) and does not feature on other previously banked H1N1 (human, avian), H3N2 (human, swine) or H5N1 (human, swine, avian). We may be looking at a series of in-situ, cross-segment Hemagglutinin genetic selections due to TamiFlu pressure, in addition to the H275Y on the Neuraminidase. We would suggest a careful examination of the samples at the Chinese boarding schools for sub-clonal minor populations carrying H275Y on the NA.

The NA of Quebec147365 is an exact amino acid match (469/469) with Denmark528, HK2369, Yamaguchi22, Hunan SWL3, Singapore57, Tokushima2 and Iwate3.  Quebec147365 is also an exact nucleotide level match to Denmark528 and Iwate3.

On Quebec147365 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 twelve 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, Iwate3, Quebec147365

Until the 2009-08-21 deposit of the two Washington sequences, all 275Y TamiFlu-Resistant specimens on PF11 backgrounds were paired with 106I.  We continue to see only 3 of the 11 with 106V.

The addition of Quebec147365 heavily leverages position 248 toward Aspartate (D) with 8 specimens versus 4 with Asparagine (N). No TamiFlu Resistant specimen on file displays 286G as yet.

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