HA syn413K and NA syn407V Cross Segment Linkage Increases Range and Penetration

Cross-Linked Silent HA and NA Polymorphisms Correlated with Fatal 225G Cases in the Ukraine and Russia
  • HA:syn413K encoded from A1281G, AAa->AAg
  • NA:syn407V encoded from T1221C, GTt->GTc
 PF11 Sequences Demonstrating Cross Segment Linkage
  • Iraq8529E3 *
  • Iraq8529M1 *
  • Iraq8531 *
  • Australia Victoria2129 with potential H5N2 inclusions and NA 454S *
  • Australia Victoria2130 with NA 454S *
  • Ukraine Kyiv377 with mixture of 225D, 225G, 225N, 225S, 225T and 225A
  • Ukraine Lviv673
  • Ukraine Lviv682
  • Ukraine Cherkasy332 *
  • Ukraine Cherkasy333 *
  • Ukraine Cherkasy346 *
  • Ukraine Dnipropetrovsk260 *
  • Ukraine Dnipropetrovsk267 *
  • Ukraine Dnipropetrovsk268 *
  • Ukraine Dnipropetrovsk272 *
  • Ukraine Dnipropetrovsk273 with mixture of wt 225D and 225G *
  • Ukraine Dnipropetrovsk274 *
  • Ukraine Dnipropetrovsk1124 *
  • Ukraine Dnipropetrovsk1171 *
  • Ukraine LvivN2
  • Ukraine LvivN6
  • Ukraine TernopilN10
  • Ukraine TernopilN11
  • MoldovaG120 *
  • MoldovaG140 *
  • MoldovaG181 *
  • MoldovaG182 *
  • MoldovaG191 *
  • HA and NA Norway2924 with mixture of wt 225D and 225G
  • HA and NA Norway3364-2
  • HA and NA CatNS7362 TamiFlu Resistant
  • HA and NA CatS1096
  • HA and NA CatS1162
  • HA and NA CatS1179
  • HA and NA CatS1181
  • HA and NA CatS1267
  • HA and NA CatS1268
  • HA and NA CatS1402
  • HA and NA CatS1501
  • HA and NA CatS1687
  • HA and NA CatS1748
  • HA and NA CatS1751
  • HA and NA CatS1761
  • HA and NA CatS1827
  • HA and NA CatS1935 *
  • HA and NA Guangdong02
  • HA and NA Guangdong05
  • HA and NA SingaporeON1156
  • HA and NA Stockholm31
  • HA and NA Russia14
  • HA and NA Russia19
  • HA and NA Russia74
  • HA and NA Russia165
  • HA and NA Russia178
  • HA and NA Russia190
  • HA and NA Russia191
  • HA and NA Omsk02 
  • HA and NA Tver2969 with 225G, Fatal outcome *
  • HA and NA Salekhard01 with 225G, presumptive Fatal outcome
  • HA and NA Orenburg2974 with 225N, potential Fatal outcome
  • HA and NA NY3702
  • HA and NA NY3715
  • HA and NA NY3828
  • HA and NA RhodeIsland08
  • HA and NA Texas42102708
  • HA and NA Texas45072128
  • HA and NA Texas45122886
  • US Private Sequence TamiFlu Resistant  
68 sequences have encircled the globe as of 2010-01-18 * with high fidelity carrying a cross-segment paired set of background markers matching and potentially contributing to the Ukraine fatal cases.  Kyiv377 from early November in the Ukraine demonstrates a level of hyper-morphic behaviour at amino acid 225 that is previously undocumented in ΣPF11, but is the natural progression of the genetic acquisition trend line on this pandemic reservoir.  Two sequences now additionally demonstrate the TamiFlu Resistant 275Y on NA, one from Spain in late November 2009 and one from the US with details stored in a private database. 

Moldova, a neighbor of the Ukraine, demonstrates extensive NA syn407V, but is missing the HA area for the syn413K on most sequences.  5 of 7 from Moldova with complete HA sequences display the cross segment linkage.

Expect to see many sequences from the Ukraine on this particular background when HA and NA are deposited for review as most of the recent published Hemagglutinins do carry the syn413K and the published Neuraminidase match the syn407VChernihiv452 from the Ukraine with a mixture of 225D, 225G, 225N and 225S carries the syn413K, but has no NA published.  A more comprehensive deposit of these two antigenic gene segments (HA and NA) from the Ukraine would allow a definitive conclusion.

Areas covered include Texas (3), the Northeastern United States (4), China (2), Singapore, Australia (2), the Ukraine (18),  Moldova (5), Russia (11), Iraq (3), Norway (2), Sweden and extensive penetration in Spain (15 sequences).  This particular background pattern may precurse 225G and mixtures of 225D / 225G.  If LvivN6 is officially confirmed as a vaccine escape event, these cross-segment pairs may be surveilled as potential future effectors of vaccine efficacy failure.

Publication of the remaining Neuraminidase segments for the 33 Norwegian and Japanese specimens bearing HA syn413K would allow a more precise review.  Although 9 of the recent sequences from Norway carry syn413K, none of the 225E strains from Norway have the syn413K.  The patterns are highly suggestive that all of the Norse 225G strains do.  The 2009-12-29 release of the NA for Norway2924 confirmed that previous suggestion.

The Orenburg2974 sequence from Russia also carries 225N on this background.  Bryansk2971, also from Russia with presumably fatal 225G from the lung, demonstrates the syn413K but has no entry for the Neuraminidase to confirm this cross segment linkage.

If RBS revisions at amino acid 225 are, in fact, instructive of high pathogenicity, then Russia is in the FlightPath for a more virulent winter and the Ukraine has presently built a fog of miasma that appears to be capable of spreading across the globe.

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