Mexico Evaluates Upper Respiratory Swabs from Fatal and Severe Cases with 225A, 225G, 225N & 225V

Sequences discussed in this analysis are variously stored publicly at GenBank and at GISAID. We gratefully acknowledge the authors, originating and submitting laboratories of the sequences from GenBank and from GISAID’s EpiFlu™ Database on which this research is based. A GISAID-generated list is detailed in a linked spreadsheet for completeness in citation.

Last Update
2011-11-03

On 2011-10-27, the Instituto Nacional de Enfermedades Respiratorias from the Centro de Investigacion en Enfermedades Infecciosas of Mexico deposited a group of human pH1N1 sequences at GenBank and GISAID.  The deposit is composed of HA segments, 14 sequence fragments of 232 amino acids (aa38 to aa269), each documenting roughly 41% of a full pH1N1 Hemagglutinin segment.  Various homology to Clade1.Upsilon exists on 5 of the sequences.

This Mexican genetic data supports an investigation entitled, H1N1pdm HA D222 variants associated with severity and mortality in patients during a second wave in Mexico and their pathogenicity in mouse model.  Mexico City, Mexico is the geography indicated on the sequence names.  Each sequence is annotated with gender and isolation source (nasopharyngeal swab), while 12 of the 14 also indicate the subject age.  Subject ages range from 23 to 54 years old, all outside the general severity range for seasonal influenza (under 2 years old or over 60 years old).  The sample dates span 2009-10-01 to 2010-04-05 with no case-level specification of treatment protocol, clinical progression or clinical outcome.

The severity and fatality correlation in cases with polymorphisms at amino acid position 222 (aa225 in H3 numbering) was established very early in the pandemic.  The issue of sample location has been repeatedly posed, with ongoing discussion that samples taken from the lower respiratory tract are more probable to produce valid evidence of aa225 revisions.  This INER deposit, relying entirely on upper respiratory swabs, documents cases where aa225 revisions are found in the upper airway.  The individual details of clinical progression and outcome (severe v. fatal) will establish measurable correlation to the upper respiratory sample location.

Four of the samples show multi-nucleotide ambiguity at amino acid position 225 (contiguous mixed traces, residues 715 and 716) producing a codon of rrT.  That sequencing outcome of rrT demonstrates the presence of wild type D225 with both 225G and 225N, hypermorphism at a single amino acid position.  Overall, ten of the fourteen sequences demonstrate a mixed peak (ambiguity) at one or more nucleotides that build aa225.  MexicoCityINER3_NP_47M_2009_10_15 [EPI341034] illustrates the highly variant nature of the pH1N1 reservoir Receptor Binding Site aa225 with two rare values, 225A and 225V, in a mixture without wild type (D225) and with no additional polymorphisms.

Sequences

. . . . MexicoCityINER14_NP_xF_2010_04_05 (
. . . . . . . . Clade1.Upsilon Potential Precursor
. . . . . . . . GISAID HA EPI341023
. . . . . . . . 8 Polymorphisms (4 Amino and 4 Silent)
. . . . . . . . HA Truncated before aa38,
. . . . . . . . syn71E (GAg) mix wt [H6N1],
. . . . . . . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . syn100D (GAc) [H1N1 Avian Farm],
. . . . . . . . 165N,
. . . . . . . . 181S,
. . . . . . . . 189T,
. . . . . . . . syn198A (GCg) mix wt,
. . . . . . . . syn213F (TTt),
. . . . . . . . 225G mix wt,
. . . . . . . . HA Truncated after aa269)

. . . . MexicoCityINER13_NP_48F_2010_03_25 (
. . . . . . . . Clade1.Upsilon Potential Precursor
. . . . . . . . GISAID HA EPI341024
. . . . . . . . 6 Polymorphisms (5 Amino and 1 Silent)
. . . . . . . . HA Truncated before aa38,
. . . . . . . . 165N,
. . . . . . . . 189T,
. . . . . . . . syn213F (TTt),
. . . . . . . . 225G mix wt,
. . . . . . . . 225N mix wt,
. . . . . . . . 225S mix wt,
. . . . . . . . HA Truncated after aa269)

. . . . MexicoCityINER12_NP_37M_2010_03_23 (
. . . . . . . . GISAID HA EPI341025
. . . . . . . . 2 Polymorphisms (2 Amino and 0 Silent)
. . . . . . . . HA Truncated before aa38,
. . . . . . . . 122R,
. . . . . . . . 225N,
. . . . . . . . HA Truncated after aa269)

. . . . MexicoCityINER11_NP_34F_2010_02_09 (
. . . . . . . . GISAID HA EPI341026
. . . . . . . . 2 Polymorphisms (1 Amino and 1 Silent)
. . . . . . . . HA Truncated before aa38,
. . . . . . . . syn214K (AAa) [H9N2],
. . . . . . . . . . . . . . . . . . [H13N2 Avian],
. . . . . . . . 225G mix wt,
. . . . . . . . HA Truncated after aa269)

. . . . MexicoCityINER10_NP_39M_2010_02_09 (
. . . . . . . . Clade1.Upsilon Potential Precursor
. . . . . . . . GISAID HA EPI341027
. . . . . . . . 4 Polymorphisms (2 Amino and 2 Silent)
. . . . . . . . HA Truncated before aa38,
. . . . . . . . syn58C (TGc) [H2N3, H3N8, H4, H6],
. . . . . . . . . . . . . . . . . [H7N3, H7N7],
. . . . . . . . . . . . . . . . . [H9N2, H11],
. . . . . . . . . . . . . . . . . [H13N2, H13N3, H13N6, H13N8, H13N9 Avian],
. . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . 189T,
. . . . . . . . syn213F (TTt),
. . . . . . . . 225G,
. . . . . . . . HA Truncated after aa269)

. . . . MexicoCityINER8_NP_23F_2009_11_23 (
. . . . . . . . GISAID HA EPI341029
. . . . . . . . 3 Polymorphisms (1 Amino and 2 Silent)
. . . . . . . . HA Truncated before aa38,
. . . . . . . . syn106E (GAa) [H1N1 Avian],
. . . . . . . . syn189A (GCc),
. . . . . . . . 225G,
. . . . . . . . HA Truncated after aa269)

. . . . MexicoCityINER9_NP_49M_2010_01_18 (
. . . . . . . . GISAID HA EPI341028
. . . . . . . . 1 Polymorphisms (1 Amino and 0 Silent)
. . . . . . . . HA Truncated before aa38,
. . . . . . . . 225G mix wt,
. . . . . . . . HA Truncated after aa269)

. . . . MexicoCityINER7_NP_54F_2009_11_09 (
. . . . . . . . Clade1.Upsilon Potential Precursor
. . . . . . . . GISAID HA EPI341030
. . . . . . . . 3 Polymorphisms (3 Amino and 0 Silent)
. . . . . . . . HA Truncated before aa38,
. . . . . . . . 157T,
. . . . . . . . 165N,
. . . . . . . . 225G,
. . . . . . . . HA Truncated after aa269)

. . . . MexicoCityINER6_NP_22F_2009_11_06 (
. . . . . . . . GISAID HA EPI341031
. . . . . . . . 3 Polymorphisms (1 Amino and 2 Silent)
. . . . . . . . HA Truncated before aa38,
. . . . . . . . syn106E (GAa) [H1N1 Avian],
. . . . . . . . syn189A (GCc),
. . . . . . . . 225G mix wt,
. . . . . . . . HA Truncated after aa269)

. . . . MexicoCityINER5_NP_52F_2009_10_27 (
. . . . . . . . GISAID HA EPI341032
. . . . . . . . 1 Polymorphisms (1 Amino and 0 Silent)
. . . . . . . . HA Truncated before aa38,
. . . . . . . . 225G mix wt,
. . . . . . . . HA Truncated after aa269)

. . . . MexicoCityINER4_NP_xM_2009_10_16 (
. . . . . . . . GISAID HA EPI341033
. . . . . . . . 4 Polymorphisms (3 Amino and 1 Silent)
. . . . . . . . HA Truncated before aa38,
. . . . . . . . syn145K (AAg),
. . . . . . . . 225G mix wt,
. . . . . . . . 225N mix wt,
. . . . . . . . 225S mix wt,
. . . . . . . . HA Truncated after aa269)

. . . . MexicoCityINER3_NP_47M_2009_10_15 (
. . . . . . . . GISAID HA EPI341034
. . . . . . . . 2 Polymorphisms (2 Amino and 0 Silent)
. . . . . . . . HA Truncated before aa38,
. . . . . . . . 225A mix,
. . . . . . . . 225V mix,
. . . . . . . . HA Truncated after aa269)

. . . . MexicoCityINER2_NP_44F_2009_10_12 (
. . . . . . . . GISAID HA EPI341035
. . . . . . . . 3 Polymorphisms (3 Amino and 0 Silent)
. . . . . . . . HA Truncated before aa38,
. . . . . . . . 225G mix wt,
. . . . . . . . 225N mix wt,
. . . . . . . . 225S mix wt,
. . . . . . . . HA Truncated after aa269)

. . . . MexicoCityINER1_NP_40M_2009_10_01 (
. . . . . . . . Clade1.Upsilon Potential Precursor
. . . . . . . . GISAID HA EPI341036
. . . . . . . . 4 Polymorphisms (4 Amino and 0 Silent)
. . . . . . . . HA Truncated before aa38,
. . . . . . . . 165N,
. . . . . . . . 225G mix wt,
. . . . . . . . 225N mix wt,
. . . . . . . . 225S mix wt,
. . . . . . . . HA Truncated after aa269)

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225A Appears In Madrid Spain Pandemic Influenza

The very effective contributors to The NIAID Influenza Genome Sequencing Consortium deposited a contemporaneous set of sequences at GISAID this week covering a significant number of data points over geography and emerging trends in pandemic RnR * polymorphism.

225A is found for the first time on an unmixed trace in this pandemic on Madrid296_2009_11_17, having previously been discussed on an unusual sequence from the Ukraine. The HA of UkrKyiv377_2009_11_07_xL only revised at two protein positions, the syn413K for cross-linkage and amino residue 225 (rvT coding up to 6 values).  These multiple, mixed traces at the first and second nucleotides of the codon represent the only documented prior instance of potential 225A in this pandemic reservoir.

Additionally, a narrow slice of the data in this directed review further suggests a peculiar behaviour that our team has postulated in the past 3 months within this present pandemic reservoir (PF11). Spain and Greece provide an active working ground for this particular genetic acquisition cycle behaviour.

Notice that the reservoir appears to individually conserve polymorphisms on strains having few revisions (generalised / consensus strains) from time to time, even after the given polymorphism has appeared on a significant count of sequences having numerous polymorphisms.  This apparent reversal of progressive genetic acquisition may have purpose. 

Preservation behaviour for future recombination using / by creating a type of "universal donor" template is suggested.  This step-wise method of storing an important piece of data for later usage in a labile format is not entirely novel in biology.  Ease of access / transfer / adoption may be increased as a function of the homology / identity of the two interchanging viral strains.  “Mix and match” becomes more organised and discrete in this scenario. Ergo, a generalised virus with only a single revision or a minimal revision count may be more successful as an overlay for material transfer.

Note that Madrid300_2009_11_30 carries only the 373H.  Similarly, notice that syn372Q (in a similar domain) is found on Russian fatality sequences that have no change other than the cross-linkage syn413K.  The syn372Q is also found upon a 225G and a fatal 225N case in the same area, Ulyanovsk. 

Is a similar function within the same sequence area (372, 373) being preserved in Spain, Greece, Portugal, Belgium, Germany and Australia using the 373H?

Is the Madrid296_2009_11_17 pairing of 225A (in its first recorded occurrence) with 373H another of the reservoir's conservation storage templates that will be referenced for later antigenic escape?

. . . . Athens357_2009_12_26 (
. . . . . . . . 1S,
. . . . . . . . 92M,
. . . . . . . . syn181G [H9N2],
. . . . . . . . . . . . . . . [Lisboa2_2010_01_04,
. . . . . . . . . . . . . . . Rome632_2009_11_23, et al],
. . . . . . . . 373H [Perth500_2010_02_17 with 165N,
. . . . . . . . . . . . . Tessenderlo191_2009_12_15
. . . . . . . . . . . . . . . . . . . . . with 165R, syn181G,
. . . . . . . . . . . . . Lisboa171_2009_12_02])

. . . . Athens358_2009_12_26 (
. . . . . . . . syn179L (CTt) [TexasJMS404_2010_01_08 (tTA)
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . with syn66G,
. . . . . . . . . . . . . . . . . . . . . Netherlands2143_2009_11_16 (tTA),
. . . . . . . . . . . . . . . . . . . . . Odense143_2009_11_11 (tTA)
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . with 48K, 269V,
. . . . . . . . . . . . . . . . . . . . . UkrPoltava746_2009_11_09_f (tTA),
. . . . . . . . . . . . . . . . . . . . . UkrCherkasy745_2009_11_01_f (tTA),
. . . . . . . . . . . . . . . . . . . . . Antwerp221_2009_10_28 (tTA)
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . with 259T,
. . . . . . . . . . . . . . . . . . . . . JapanAF2244_2009_10_14 (CTg),
. . . . . . . . . . . . . . . . . . . . . ColoradoAF2139_2009_10_06 (CTg)
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . with syn311K, 324I,
. . . . . . . . . . . . . . . . . . . . . NY4981_2009_10_05 (CTg)
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . with syn311K, 324I,
. . . . . . . . . . . . . . . . . . . . . ThailandPMKD0030_2009_09_25 (tTA),
. . . . . . . . . . . . . . . . . . . . . WiscS0143_2009_06_02 (CTg),
. . . . . . . . . . . . . . . . . . . . . WiscD1725_2009_06_01 (CTg),
. . . . . . . . . . . . . . . . . . . . . WiscD0117_2009_05_28 (CTg)]
. . . . . . . . 373H [Perth500_2010_02_17 with 165N,
. . . . . . . . . . . . . Tessenderlo191_2009_12_15
. . . . . . . . . . . . . . . . . . . . . with 165R, syn181G,
. . . . . . . . . . . . . Lisboa171_2009_12_02])

. . . . Munich364_2009_12_04 (
. . . . . . . . #1V,
. . . . . . . . syn181G [H9N2],
. . . . . . . . . . . . . . . [Lisboa2_2010_01_04,
. . . . . . . . . . . . . . . Rome632_2009_11_23, et al],
. . . . . . . . 373H [Perth500_2010_02_17 with 165N,
. . . . . . . . . . . . . Tessenderlo191_2009_12_15
. . . . . . . . . . . . . . . . . . . . . with 165R, syn181G,
. . . . . . . . . . . . . Lisboa171_2009_12_02],
. . . . . . . . syn396V,
. . . . . . . . syn477T)

. . . . Munich363_2009_11_30 (
. . . . . . . . 165R [Tessenderlo191_2009_12_15
. . . . . . . . . . . . . . . . . . with syn181G],
. . . . . . . . syn181G [H9N2],
. . . . . . . . . . . . . . . [Lisboa2_2010_01_04,
. . . . . . . . . . . . . . . Rome632_2009_11_23, et al],
. . . . . . . . 373H [Perth500_2010_02_17 with 165N,
. . . . . . . . . . . . . Tessenderlo191_2009_12_15
. . . . . . . . . . . . . . . . . . . . . with 165R, syn181G,
. . . . . . . . . . . . . Lisboa171_2009_12_02],
. . . . . . . . syn488D,
. . . . . . . . syn514Y)

. . . . Madrid300_2009_11_30 (
. . . . . . . . 373H [Perth500_2010_02_17 with 165N,
. . . . . . . . . . . . . Tessenderlo191_2009_12_15
. . . . . . . . . . . . . . . . . . . . . with 165R, syn181G,
. . . . . . . . . . . . . Lisboa171_2009_12_02])

. . . . Madrid299_2009_11_26 (
. . . . . . . . 128I,
. . . . . . . . 235I,
. . . . . . . . 373H [Perth500_2010_02_17 with 165N,
. . . . . . . . . . . . . Tessenderlo191_2009_12_15
. . . . . . . . . . . . . . . . . . . . . with 165R, syn181G,
. . . . . . . . . . . . . Lisboa171_2009_12_02],
. . . . . . . . syn453R)

. . . . Madrid298_2009_11_24 (
. . . . . . . . 0I [H9N2],
. . . . . . . . .  [Lisboa2_2010_01_04,
. . . . . . . . . Latvia12_649_2009_12_09,
. . . . . . . . . NY7426_2009_12_08,
. . . . . . . . . Tambov_FOS_2009_12_01_xL,
. . . . . . . . . Slovenia5555_2009_12,
. . . . . . . . . Slovenia5559_2009_12,
. . . . . . . . . Ivanovo_RNA_2009_11_24_xL_f with 225G, 225N,
. . . . . . . . . Stockholm107_2009_11_24,
. . . . . . . . . GD_Yuncheng51_2009_11_19,
. . . . . . . . . Guangdong1271_2009_11_19,
. . . . . . . . . Austria528378_2009_11_19,
. . . . . . . . . Latvia11_1133_2009_11_16,
. . . . . . . . . Latvia11_1133M_2009_11_16,
. . . . . . . . . Latvia11_575_2009_11_11,
. . . . . . . . . England94600039_2009_10_27,
. . . . . . . . . SwedenUmea8_2009_10_07,
. . . . . . . . . Managua2323_02_2009_08_18,
. . . . . . . . . Utah20_C2_2_2009_07_25_VxX with 159D, 227G,
. . . . . . . . . Texas42163291_2009_06_16,
. . . . . . . . . Marseille3416_2009],
. . . . . . . . syn181G [H9N2],
. . . . . . . . . . . . . . . [Lisboa2_2010_01_04,
. . . . . . . . . . . . . . . Rome632_2009_11_23, et al],
. . . . . . . . 233H [NC Duke TmX Fatality cluster,
. . . . . . . . . . . . Rome632_2009_11_23 with syn181G],
. . . . . . . . 373H [Perth500_2010_02_17 with 165N,
. . . . . . . . . . . . . Tessenderlo191_2009_12_15
. . . . . . . . . . . . . . . . . . . . . with 165R, syn181G,
. . . . . . . . . . . . . Lisboa171_2009_12_02],
. . . . . . . . 504N [England735_2009_10,
. . . . . . . . . . . . England1023_2009_09,
. . . . . . . . . . . . England (11),
. . . . . . . . . . . . Scotland94420091_2009_08_11])

. . . . Madrid296_2009_11_17 (
. . . . . . . . 225A [Unique to PF11],
. . . . . . . . 373H [Perth500_2010_02_17 with 165N,
. . . . . . . . . . . . . Tessenderlo191_2009_12_15
. . . . . . . . . . . . . . . . . . . . . with 165R, syn181G,
. . . . . . . . . . . . . Lisboa171_2009_12_02])

Please refer to additional studies for further genetic analyses, including the survey on amino acid revisions potentially related to Vaccine Escape.  A hyper-morphic, TamiFlu-resistant sequence from the state of Washington in Spring 2010 has recently been profiled with similar zoonotic influences.


* Rare, not Random.

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The Ukraine Trends Toward 1,000 Fatalities by Mid-January; 225 Diversity Increases

If the present daily rate of deaths continues for the short term, the Ukraine will reach 1,000 fatalities by the middle of January, approximately 75 days from the start of the flashfire.  Their official report on January 5 showed a one day increase of 100,000 new cases.  You may recall the rapidity with which this country reached 1 million infections.

The United States with a population of 300 million reached 1,000 official fatalities roughly 6 months after the initial deaths were recorded and the new viral reservoir was identified.  We remind you that the Ukraine has a population roughly one-sixth (17%) of the United States at just under 50 million citizens. 

• 1,000 deaths from 300 million in roughly 175 days = United States
• 1,000 deaths from   50 million in roughly   75 days = Ukraine

Perhaps some type of acceleration is presently at work.

As GeneWurx.com is tracking the emergence of Receptor Binding Site polymorphisms and epitope acquisitions in relation to published epidemiological and clinical accounts, the Ukraine continues to offer the most comprehensive picture and the most up-to-date information. Coupled with the recent publication of sequences from Russia and Turkey that correspond in various areas with the Ukraine’s early sequence deposit (225 diversity, HA syn413K and NA syn407V) and the additional interlacing of that same superset of related sequences (Ukraine, Russia, Turkey) with Spain, US and Chinese PF11 and H5N1 genetic markers, the present acceleration of cases and deaths in the Ukraine should be closely monitored.

The most recent sequences published from the Ukraine are partial and were sampled in November just as the wave reached 1 million cases.  Slightly under 4 million cases are presently reported.  4 million cases should generate more than the 23 partial sequences now published?

The most recent sample from Kiev yielded the nucleotide sequence of RVT at amino acid 225 potentially coding for 6 distinct amino acid values. R and V are Ambiguity Codes indicating mixed peaks on the sequencing trace. The R at the first base of the codon demonstrates that two values were documented. The V at the second base of the codon indicates that three distinct values were detected.

R = A and G
V = A, C and G
T = T

AAT = 225N
ACT = 225T
AGT = 225S
GAT = 225D wt
GCT = 225A
GGT = 225G

A sample from Chernihiv yielded the nucleotide sequence of RRT coding for 4 potential values at amino acid 225. The R at the first base of the codon demonstrates that two values were documented. The R at the second base of the codon indicates that the same two distinct values were detected there as well.

R = A and G
R = A and G
T = T

AAT = 225N
AGT = 225S
GAT = 225D wt
GGT = 225G

The most recent group of sequences (November) continues a strong correlation to the early cross segment linkage background and persists in accelerated genetic variation at position 225. The two sequences that demonstrate Receptor Binding Site diversity show significant single amino acid position variation on a level unprecedented in ΣPF11. 

Outside the RBS, this Ukraine background for presumably fatal cases appears to be strikingly stable, balancing strong genetic throw against very minimal position variation (225) arguably for immune escape and vaccine escape.  This emerging sub-clade may represent a new base point for the virus in that region, becoming a universal donor of sorts to the surrounding countries as seen in Russia and Turkey.

Just as PF11 has replaced seasonal influenza around the world, this cross segment linkage background appears to be supplanting the various versions from ΣPF11 in this region. If the cross linked silent Ukraine changes are correlated as a platform for RBS diversity at 225 and 225G/225N/225E are associated with fatality cases around the world, future fatality increases may be predictable based on the geographic extent of that cross linked background (HA syn413K and NA syn407V). 

Will the Ukraine be historically noted in some epidemiology paper of the distant future as the incubator for a new and powerful sub-clade under ΣPF11?  Is that the best we can do?  Or will we take the present trend for the full value of the data and proact today by illuminating the lab day and night with the best gear, the most definitive techniques and the brightest scholars, driving for an actionable answer?

The death count nears 1,000 in the Ukraine over a very short time span and the sequences from that country and neighboring areas indicate hyper-morphic behaviour at amino acid position 225.  No interpretation required.

Gather and Solve.

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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 syn407V.  Chernihiv452 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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