US Capital, New York and Wisconsin Add 15 Recent Samples to the Cross-Linked Background

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  with HA 131L, 160L, 194I, 298V and syn419L (Kentucky19 and 225G Utah42)
• Iraq8529M1 with HA 131L, 160L, 298V and syn419L (Kentucky19 and 225G Utah42)
• Iraq8531     with HA 130E, 131L, 298V and syn419L (Kentucky19 and 225G Utah42)
• 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 Chernihiv855L with mixture of wt 225D / 225G and additional 1918 Markers (syn238E & 324I), Fatal outcome 
• Ukraine Chernihiv856 with mixture of wt 225D / 225G , Fatal outcome 
• Ukraine Chernihiv857 with mixture of wt 225D / 225G and additional 1918 Markers (186P, syn238E, 324I & G796A), Fatal outcome 
• Ukraine Chernihiv858, Fatal outcome 
• 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 with 225G
• Ukraine LvivN6 with 225G
• Ukraine TernopilN10 with 225G
• Ukraine TernopilN11 with 225G
• Ukraine Volin226 with 225G
• MoldovaG120
• MoldovaG140
• MoldovaG181
• MoldovaG182
• MoldovaG191
• HA and NA Norway2924 with mixture of wt 225D and 225G
• HA and NA Norway3364-2
• HA and NA Denmark AarhusINS82 with syn177L and 324I
• HA and NA Denmark CopenhagenINS95 with 69K, syn157K and 176I
• HA and NA Denmark CopenhagenINS98
• HA and NA Poland WarsawINS100 with 324I and 377K
• HA and NA Greece AthensINS85 with syn57C, syn233Y, 324I and 377K
• 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 CatS2120 with multiple swine markers
• HA and NA CatS2151 with swine markers and 165N (TamiFlu Resistant CatNS7632 and Russian 225G Salekhard01)
• HA and NA Guangdong02
• HA and NA Guangdong05
• HA and NA SingaporeON1156
• HA and NA India BloreNIV236 with 226R, syn372Q, 454N and 550T
• HA and NA Sweden Stockholm31
• Sweden Malmoe1 from 2010 with 190Y, 324I and 377K
• Sweden Gothenburg2 with 146G, 324I (1918) and markers found extensively in Moldova and Russia 
• HA and NA Russia4 with syn238E and 324I (1918)
• HA and NA Russia12 with 324I (1918)
• HA and NA Russia14
• HA and NA Russia19 with 324I (1918)
• HA and NA Russia74
• HA and NA Russia149
• HA and NA Russia165
• HA and NA Russia171 with 165N
• HA and NA Russia178
• HA and NA Russia180 with 165N, syn239P and 264G
• HA and NA Russia190
• HA and NA Russia191
• HA and NA Kurgan01 with HA 214E (MoldovaG168, G176, G188) and NA mixture at 407 (Fatal 225G Abakan02) 
• HA and NA Omsk02 
• HA and NA Tver2969 with 225G, Fatal outcome
• HA and NA Salekhard01 with 165N and 225G, presumptive Fatal outcome
• HA and NA Orenburg2974 with 225N, potential Fatal outcome
• HA and NA Perm01 with 131P, 225G and 324I, presumptive Fatal outcome
• HA and NA District of ColumbiaINS43 with 22I, syn157K and 176I *
• HA and NA NY3702
• HA and NA NY3715
• HA and NA NY3828
• HA and NA NY4398 *
• HA and NA NY4977 with 189T *
• HA and NA NY5086 with 22I, syn157K, 176I and 264T *
• HA and NA NY5186 *
• HA and NA NY5227 with 189T *
• HA and NA NY5931 with 22I, syn157K, 176I and 262K *
• United States NewYork96
• HA and NA RhodeIsland08
• HA and NA Texas42102708
• HA and NA Texas45072128
• HA and NA Texas45122886
• HA and NA WiscD0544 with 22I, syn157K and 176I *
• HA and NA WiscD0853 with 22I, syn157K, 176I, 188I, 231K and 277N *
• HA and NA WiscD1915 with 22I, syn157K, 176I, 188I, 231K and 277N *
• HA and NA WiscD1987 with 189T and 324I *
• HA and NA WiscD2060 with 22I, syn157K and 176I *
• HA and NA WiscD2337 with 22I, syn157K, 176I, 188I, 231K, 277N and 285S *
• HA and NA WiscS1252 with 189T and 324I *
• HA and NA WiscS1416 with 22I, syn157K, 176I, 188I, 231K, 277N and syn366A *
• United States Kentucky19 from an 18 year old subject with HA 298V
• United States Indiana20 from a 10M subject with 5 Avian H5N1 markers
• US Private Sequence TamiFlu Resistant  
• United States NorthCarolina37 from a 24F subject with HA 298V
• United States NorthCarolina44 from a 50M subject with 6 Avian H5N1 markers
• United States NorthCarolina46_C2     from a 39F subject with HA 298V
• United States NorthCarolina46_C2C1 from a 39F subject with HA 298V
• HA and NA swine/NC/34752 with 298V 
• HA and NA swine/OR4060 Emergent Non-PF11 Lineage of H1N1 2009-12-31 *

113 sequences have encircled the globe as of 2010-03-24 * with high fidelity carrying a cross-segment paired set of background markers matching and contributing to fatal cases in the Ukraine and Russia.  225G appears in 14 on this background; 225N once and 225E precisely zero.  The first occasion of 226R entered the list this week retrospectively due to sequence release delay with a June 2009 case from India.

The 15 newest entries represent a diverse geography within the United States of ΣPF11 infections, including 1 entry for Washington D.C., the nation's capital, 6 from New York and 7 from Wisconsin.  The final entry is an H1N1 swine from Oregon that documents an emergent non-PF11 lineage building onto this cross segment linkage.

The available data, though sparse, requires the simple evaluation that this pandemic reservoir is not approaching stasis. The background continues to widen within the existing clades adding polymorphisms from H5N1 and 1918 strains demonstrating that ΣPF11 is far from reaching Omega status.   Movement onto this cross-linked background has accelerated recently, now encompassing 2% of all available pandemic sequences.

Areas covered include Texas (3), the Northeastern United States (11), Wisconsin (7), Oregon, Washington D.C., Kentucky, Indiana, North Carolina (5), China (2), Singapore, India, Australia (2), the Ukraine (23), Moldova (5), Russia (18), Iraq (3), Denmark(3), Norway (2), Sweden (3), Poland, Greece and extensive penetration in Spain (17 sequences).

Receptor Binding Site (RBS) changes at 225 are associated with fatality, 225G and 225N at a rate higher than 225E.

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.

Previous Study on this Topic:

• 2010-03-22 Cross-Linked Background Includes 226R Strain from India and Sweden Entry with novel 190Y
• 2010-03-17 Cross-Linked Background Supporting Fatal 225G Cases Penetrates 3 New Countries: Poland, Denmark and Greece
• 2010-01-28 Ukraine - 100% of New Sequences with Required HA and NA on Cross-Linked Background; 225G on 6 of 11; 1918 Markers Coalesce
• 2010-01-19 Fatal Ukraine Cross Segment Linkage Extends in the US, Iraq and Australia (HA syn413K and NA syn407V)
• 2010-01-01 HA syn413K and NA syn407V Cross Segment Linkage Increases Range and Penetration
• 2009-12-04 Spain Introduces 2 November Sequences with Cross-Segment Pairing from Fatal Cases in the Ukraine
• 2009-11-28 Ukraine and Spain Cross-Linked HA and NA Silent Changes Circle the Globe
• 2009-11-26 The Ukraine, Norway and Spain Share Paired HA and NA Changes

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