Sweden Deposits 225G with Alternate Coding Matching and Pre-dating Norway3206-3 with NA Marker Homology

Sweden deposited a sequence today from mid summer that carries indicators worthy of study.

Matches include the rare alternate coding for 225G found in the Norway3206-3 fatality sampled 6 weeks after the Swedish case and the NA syn291V on that same Norwegian sample.  Six weeks appear to be enough time for these changes to travel across borders.  The HA sequences are identical, except for the 140S on Norway3206-3.

The two Scandinavian NA segments show a shared polymorphism at syn291V, a change that is found in 103 GenBank sequences including TamiFlu Resistant HK2369, Almati01, Tomsk01, Poland and with deep penetration through Italy and Catalonia.  The G873A coding for the syn291V is also present in CatNS2001 and CatNS2008.  The NA segment of Norway3206-3 is identical to the Swedish NA.

Only this profiled private Swedish sequence from mid summer, CatNS2001 and CatNS2008 from early August and Norway3206-3 from September carry this variant Glycine coding at amino acid 225 that is seen as T717A, GGt->GGa.  Neither of the cross segment pair, HA syn413K or NA syn407V, appears in the recent Scandinavian samples. 

The Swedish sequence is a nucleotide match with Norway2674 and Norway2690 except for the RBD polymorphism 225E on the Norwegian sequences.  Dialing back the resolution by 1 nucleotide, we find that the Swedish sequence is a 1724/1726 match with 2 more Norway 225E cases, Norway3059 and Norway4023.  Delta is indicated after link to sequence.

2009-07-27  Norway2674  Δ 225E
2009-07-29  Norway2690  Δ 225E
2009-08-11  Norway3059  Δ 225E + 1 nucleotide
2009-10-14  Norway4023  Δ 225E + 1 nucleotide

If we return to the tighter resolution again, we find that the Swedish sequence is a exact nucleotide match except for the two nucleotides coding for 225D on 6 additional sequences from Sweden (1),  Germany (1) and Russia (4).  Delta is indicated after link to sequence.

2009-__-__ Bayern66         Δ 225D
2009-05-21 MoscowIIV01    Δ 225D
2009-05-30 Stockholm33    Δ 225D Traveler from US
2009-06-09 MoscowIIV04    Δ 225D
2009-06-20 MoscowIIV05    Δ 225D
2009-09-22 Russia01          Δ 225D

This particular background is far from isolated.  The homology between these 225D, 225E and 225G sequences raises a very basic question. 

Does some mechanism in the protocol from sample to sequence potentially vary the outcome or block 225G materialisation on the resultant sequence?  We know that lungs are being destroyed across extensive geography, yet few 225G sequences are being produced?  Backing studies lead us to believe that 225G bearing samples will grow well in a receptor environment rich in α2-3-linked sialic acid. 

MDCK cell lines specialised to overexpress α2-6-linked sialic acid at the expense of α2-3-linkedSA are being employed in Neuraminadase Inhibitor sensitivity testing, demonstrating that these canine cell lines are adaptable in linkedSA expression.  Exactly how sensitive is the culture environment that is being used as a predecessor to sequencing?  How consistent are the protocols and materials between labs?

Does a possibility exist that current MDCK cell lines being used are underexpressing α2-3-linked sialic acid in a manner consistent with the low numbers of resultant 225G sequences that have been published?  Are samples that are originating with 225G not growing well due to a limited ratio of matched receptors?  We specifically enquire here on the cell lines, but obviously all aspects of the growth environment must be inspected for inhibitors to 225G materialisation if the presenting sample sequences are to be accurately elicited. 

Similar rare codings across 4 geographically dispersed sequences for Glycine at HA residue 225 and an NA syn291V occurring in temporal sequence from Sweden in late summer, to Catalonia in early August, and onward to Norway on September 1^st beg for any explanation other than "spontaneous" mutation within a pandemic reservoir, ΣPF11, that is actively demonstrating an ability to share data. 

Is 225G transmitting?  Is 225G transmitting in 2 variant forms?  Is 225G now confirmed as Hydra?

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