TamiFlu Resistant Sequence #14 from Spain in Late November Carries Cross Segment Pair of Markers from the Ukraine

HA and NA CatNS7362 is the most recent official entry into the TamiFlu Resistant list of 14 sequences.  This Spanish sequence sampled 2009-11-26 from a male in Catalonia also becomes the first recorded TamiFlu Resistant strain to participate in the cross segment pairing of HA syn413K and NA syn407V.

The NA of CatNS7362 is novel at the nucleotide level with no peer within ΣPF11.  The NA is an exact nucleotide match to A/Singapore/ON1156 (2009-07-14) and A/Catalonia/S1702 (2009-11-02) except for the SNP encoding the antiviral resistance.  The 7 polymorphisms found on the HA and the NA of this sample indicate a similar hyper-morphic behaviour that we saw with the Italian TamiFlu Resistant sequence, Pavia21.  Three of the polymorphisms are silent.  Inclusions are noted that previously appear on other sequences from Spain, Swine H1N1, Swine H1N2, Avian H1N1, Human H5N1, Avian H5N1 and Avian H6N1. 

NA Amino Acid Codings to 3 Rare Polymorphisms

• syn149I
• 275Y
• syn407V

syn149I
encoded from T447C, ATt->ATc 
Rare to ΣPF11 with 2 instances from Spain and 1 from Singapore.
CatS1687
CatS1702
SingOn1156

syn407V
encoded from T1221C, GTt->GTc 
Rare to ΣPF11 with 37 instances, yet common to Spain with 15 and the Ukraine with 9.
Progenitors may include:
H5N1 Human
H5N1 Avian

On CatNS7362 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

106I is implied for CatNS7362 based on previous patterns as that portion of the sequence is truncated.

The following permutations are now represented on the fourteen 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, Pavia21, CatNS7362

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 13 with 106V.  The addition of CatNS7362 heavily leverages position 248 toward Aspartate (D) with 10 specimens versus 4 with Asparagine (N). No TamiFlu Resistant specimen on file displays 286G as yet.

HA Amino Acid Codings to 2 Novel and 2 Rare Polymorphisms

• 165N
• 235A
• 397D
• syn413K

165N
CatS1687 is the singular instance within ΣPF11.
Progenitors may include:
H1N1 Swine
H1N2 Swine
H6N1 Avian

235A
Novel to ΣPF11.
Progenitors may include:
H1N2 Swine
  Swine/Minnesota/1713/2000
  SW/MN/16356/2001
H6N1 Avian
  Chukkar (first base SNP required)

397D
Novel to ΣPF11.
Progenitors may include:
H6N1 Avian

syn413K
encoded from A1281G, AAa->AAg 
Rare to ΣPF11 with 74 instances, yet common to Spain (12), the Ukraine (4), Japan (28) and Norway (9).
Progenitors may include:
H1N1 Avian
  red-winged tinamou/Argentina/MP1/2008

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