E627K from July Discovered Retrospectively, Tied to Netherland's Vacation Island in Diabetic Patient and Adolescent Female

Though the sequences have not been released, the team at Erasmus MC in Rotterdam has done us all a great service by providing an early report of 627K in the Netherlands. 

The multiple cases all vector from visits to a popular vacation island between July 13 and August 9.  Two of the cases do not appear to be related via direct contact, potentially indicating an endemic and silent spread of a minor PF11 population carrying the human-fit virulence factor 627K in a sub-clade that may match the major circulating sub-clade there but for the Lysine recombination.  Ten of twelve (83%) sample specimens from this geography fall into this sub-clade indicating the potential for dominant circulation in that area.

As this release of information via Promed is very limited, additional evalution and insight will require amendment and revision to this article as the matter is clarified on several accounts, including specification of the E627K sequence count and the various ratios confirming the certain Hydra Effect demonstrated in the study population.

In our reading, 3 distinct cases are described in the Osterhaus release. The researchers may have mentioned “two patients” because the family contact and the younger sister may have been directly evaluated by them in a clinical setting?

• Male Diabetic who may have shared activities with ill female camper, onset 2009-08-09
• Female camper, onset after returning home 2009-07-20  
• Female family contact of ill camper, onset after camper returned on 2009-07-20
• Younger sister of female family contact, onset 2009-07-23

This highly interpretive post is preliminary based on inconclusive language in the press release.

No mention is made of the correlating PB2 virulence mediators 701N and 703K at this time in the information released.  We suspect these to be absent due to the non-fatal clinical outcomes; however, confirmation would be useful.

As the samples were examined retrospectively, little new observational evidence will be forthcoming.  Rational projections due to this 627K mid-Summer emergence in the Netherlands and the late May emergence in Shanghai71T could cause us to expect a geographically-dispersed, wild-type sub-population carrying this virulence factor.

Tenacious sub-clonal evaluation of current sequences in the United States will likely indicate mixed peaks at the PB2 residue coding for the Lysine at 627.

Please visit GeneWurx.com for insight into the latest published studies.

Influenza Flux Continues High-CFR Risk Period as PF11Ω Remains Distant

The PF11 reservoir remains within the same category as H5N1, Interferon-Deranging, Rapidly Replicating Virus (IDRRV), in our estimation. The Influenza Flux (zoonotic transition period) may be the prime driver in this categorisation for each subtype. Though High-CFR H5N1 and today’s PF11 reservoir fall into the same category based on genetic expression, one profound difference in PF11 does emerge, a particularly strong advantage for this virus.

PF11 began with several key portions of the genetic material for human fitness but remains distant from human fitness in general; the virus is most certainly still hobbled even while demonstrating destructive clinical effects in individual hosts. As a matter of record, the rate of trait-enhancing genetic acquisition is dramatically higher than in H5N1, contrary to the daily social messaging, “No Mutations” phraseology.

Perhaps this higher and very consistent rate of genetic acquisition in PF11 is due to the current distance from full human fitness?  The early foothold in partial human fitness within the reservoir remains bounded / limited by the continued shortcoming in achieving full human fitness.  The enhanced speed of acquisition may be driven by the intersection of two pandemic aspects, distance from full human fitness and the deep reservoir of donor candidates for human-fit traits.  Spark and Fuel.  Implementing a sub-category to IDRRV due to the special nature of this PF11 reservoir, IDRREAV¹, may establish useful language for further study.  Regardless of what this pandemic reservoir is called, the time period between today’s partial human fitness and the future’s fully human-fit and virulence-downrated viral emergence is mankind’s window of High-CFR danger.

Some have postulated that 1918 was 50/50 swine and human influenza genetics.  Knowledge cannot be attained to conclusively prove this bold idea because very little predecessor genetics is on record for comparison.  At this time, PF11 is genetically less than 15% human-fit by nucleotide count including the full human-based segment and the total count of potentially human-fit SNPs across the other seven gene segments.

If this viral reservoir is marching toward a 50/50 ratio as 1918 has been postulated, then today’s 1.6% to 5% CFRs may eventually be much higher than the 1918 Case Fatality Rate.  The achievement of an H5N1 CFR would entirely be conjecture at this time, but a doubling of the current PF11 median to a figure between 4% and 5% CFR is within educated consideration.  At the practical moment of PF11_Ω (PF11 Omega²), when the future dominant PF11 strain reaches the critical tipping point in the Influenza Flux where transmission is perfected and virulence peaks, a peaking CFR is a logical expectation.

We project that throughout the current Influenza Flux period prior to the critical mass of PF11_Ω, the Hydra Effect that our team has documented in the related gene studies will continue to be demonstrated with many transmissible and virulent heads (strains) developing and persisting. Eventually the post-Omega, PF11_>Ω, fully human-fit viral reservoir will coalesce, will downrate in virulence or will be replaced once the host population is depleted.

This viral reservoir progression is strikingly similar to the pattern our research team predicted 3 years ago for an emerging H5N1 pandemic, but for the fact that ΣPF11 has enhanced genetic acquisition rates demonstrating RNA gain from 5 or more Influenza serotypes.  Timing cannot be predicted with accuracy; however, the recombinations of trait-enhancing, human-fit SNPs are directly trackable and fungible as evidence of progression under this proposed framework of study.




¹ Interferon-Deranging, Rapidly Replicating, Enhanced Acquisition Virus (IDRREAV)
² Glossary Updates

ΣPF11
Sigma PF11.
In general, the PF11 Reservoir of genetic material.  Accumulation of all specimens trending to the established pandemic backgrounds.

PF11_β
PF11 Beta.
Today.  Current PF11 specimens. These strains have progressed beyond the initial Spring 2009 PF11 infections, yet continue to be only partially human-fit.

PF11_Ω
PF11 Omega.
A proposed future PF11 momentary state of peak high-transmissibility and high-virulence potentially correlating to the zenith of the High-CFR window for humans.

PF11_>Ω
PF11 Post-Omega.
A proposed future PF11 state occurring at some point after PF11_Ω, having a progressively downrated virulence and the potential for establishing a smaller set of dominant strains in the PF11 Reservoir, ΣPF11.

Please visit GeneWurx.com for insight into the latest published studies.

Wisconsin Samples from May Match Chinese Lishui01 at HA 324I

Wisconsin adds 3 sequences to the rare HA 324I reservoir discussed earlier in the Chinese Lishui01.  The samples were taken within 48 hours of each other and all come from young subjects.  324I is found on 2008 and 2009 Seasonal H1N1 backgrounds as well as early H1N1 sequences, 1918 and WSN33.

• A/Wisconsin/629-D02144 sampled 2009-05-28 from a 17 year old subject
• A/Wisconsin/629-D01833 sampled 2009-05-27 from a 27 year old subject
• A/Wisconsin/629-D00829 sampled 2009-05-28 from a 10 year old subject

324I is now found on 13 wt specimens at GenBank.

• United States (8)
• Japan (4)
• China (1)

Please visit GeneWurx.com for insight into the latest published studies.

Brasil Registers 1,024 Deaths with Argentina Above 500 Confirmed

Today, Brasil became the first country in the world to register more than 1,000 Confirmed PF11 Deaths.  Argentina follows with 514.  Two additional South American countries have continued into triple digits with Chile at 126 and Peru at 121.  Local news in Brasil reports that at least one state has 200 deaths awaiting lab confirmation.

Yet today, news stories publish disinformation stating that gene studies demonstrate no significant changes have occured in the circulating PF11 strains?

Facts may be measured and validated.  Bodies are being counted.  Genetic changes are demonstrated.

Brasil has published substantial genetic variation at positions matching 1918 and very-high CFR H5N1 strains.  Mid-Term Argentina sequences supplied by Columbia University carry significant variation.  The death counts in each country trend with these genetic acquisitions.

These Southern Hemisphere sub-clades of PF11 will be making their way northward in the coming weeks.  Bear in mind that the United States has registered 688 deaths under two exceptional situations:

1. All deaths are prior to the normal Fall onset of the "Flu Season".
2. Very few of the actual deaths have been recorded because testing was curtailed in Late May. 

How much longer will science claim stability in a virus that is rapidly acquiring genetic material?

Please visit GeneWurx.com for insight into the latest published studies.

Deaths in Brasil Match 1918 and H5N1 Receptor Binding Domain at HA 225G

Within 9 Sao Paulo sequences released today from Brasil spanning late July to mid August 2009, we find at least 6 distinct HA backgrounds of which 5 are compelling and 2 are novel to the PF11 reservoir.  Sequences from potentially expired patients are indicated boldly.  This level of genetic diversity at key antigen sites on the Hemagglutinin (HA/H1) in a single geography during a common timeframe is of great interest and, at a minimum, reflects regional Acquisition Acceleration. 

Bear in mind that in the early stages of the pandemic, PF11 exhibited extreme stability demonstrating 100% homology across entire countries.  You will find in the early record several groups of more than 400 HA and NA sequences across diverse geography that match exactly.  We are now in a new phase as the PF11 reservoir has been passaged within humans through one winter cycle in the Southern Hemisphere and has demonstrated the ability to rapidly gain beneficial genetic traits, traits that drive toward fatal outcomes.

Background1
SaoPaulo53823
2E
188I
296H

The presumably fatal case appears to be the first instance of 188I on a PF11 background.  Human-fit Seasonal Influenza from 2007, 2008 and 2009 as well as the 2001 HKswNS1569 carry 188I, including ShanghaiLWS1 with the M230I RBD polymorphism.  Movement at 188 to Asparagine (N) has occured in NY3502, Utsunomiya01 and Utsunomiya02.

Background2
SaoPaulo53838
2E
225N
296H

Background3
SaoPaulo57831
2E
296H

Backgrounds1, 2 & 3 continue the PF11 Intra-Segment exclusivity of 206T and 296H though proximal donors of 206T are available.

Background4
SaoPaulo53845
206T
225N

In addition to these two specimens from Brasil, 225N is found only on one other PF11 sequence, NY4099.  Several Korean swine carry the change.  More importantly, a linked candidate, A/swine/Hong Kong/NS1659/2001, featuring widely in PF11 Genetic Acquisition paths also carries 225N.  HKswNS1659 shows HA:188I, 189T, 252M & 261K with additional matching to the 2008-2009 Seasonal Influenza NA Triple Combination, 106I, 248N, 286G.

Background5
SaoPaulo53206, SaoPaulo53225
206T
225G

Receptor Binding Domain changes at 225 may be correlative to fatal outcomes in Brasil as 100% of these cases appear to have expired (4/4).  However, the RBD change may not be a requirement for fatality in SaoPaulo.  Of three cases carrying only the 206T revision, one (SaoPaulo54392) appears to have expired.

225G is consensus for H5N1, is carried on NewYork1918 and only appears in six other PF11 sequences across the US and Mexico.

MX3955
MXInDRE4114
NY04
GA01
TX05
TX11

225X is demonstrated several times in the US proximal to 225G in area and time.

NY11
NY31
TX10
CA13
NE02

Please visit GeneWurx.com for insight into the latest published studies.

SingaporeTLL10 HA demonstrates 3 H5N1 amino acids: 206T, 226R and 261V

A/Singapore/TLL10, sample 2009-07-27, is a first on the PF11 background.

SingTLL10 is the first on PF11 to carry 261V, though movement at that position has been documented in Italy51 and Italy53 with 261G and a downstream 263D entered PF11 with Tomsk01 and then continued with 3 Thai sequences (ThaiCU-H9, ThaiCU-B938, ThaiCU-H276).

261V is wild type for H5N1 including Anhui02 that carries all three of the amino acid changes mentioned here for SingTLL10:

• 206T
• 226R
• 261V

H5N1 Anhui02 is a potential donor for 296H that seems to track primarily to 206T bearing strains.

This expansion deeper into Southern Asia with 226R brings the number of sequences bearing the H5N1 match into double digits.  RBD changes matching H5N1 demand scrutiny.  For background, please read an earlier 226R Study.

Please visit GeneWurx.com for insight into the latest published studies.

TamiFlu Resistant Singapore57 Sequence Available at GISAID EpiFlu database; 106I, 248D, H275Y

The NA and HA for A/Singapore/57 from 2009-05-30 are again downloadable from the European EpiFlu database as GISAID has thankfully been able to re-establish scientific community access to their data.

The NA of Singapore57 is an exact nucleotide match with Denmark528. 

Furthermore, Singapore57 is a match at all positions (1409) but C823T (TamiFlu Resistance) with:

A/Wisconsin/629-D01445 (1Y, 2009-5-24)
A/Bethesda/SP508 (14F, mid June)
RhodeIsland07 (HA:296H)
Massachusetts08 (14M)
Michigan06 (14M)
NewYork (many sequences from young people)
WestVirginia01 (15M)
Texas39 (12F, late May)
Arizona05 (4F, late April)
Utah02 (8F)
Utah04 (9F, late May)
Utah11 (9M, mid June)
Nevada03 (2F, late April)
Montana06 (14M, early May)
Georgia08
Oregon20
Canada (several)
Thailand (several, mid June)
Taiwan (several)
Germany (2 including Bayern66)

The geographic range of this PF11 background is extensive, with exceptional breadth in the United States and the background correlates to young people.

TamiFlu Resistance is indicated in typical PF11 fashion via a Single Nucleotide Polymorphism on Singapore57 coding for 275Y on the Neuraminidase. The sequence displays the following NA Quadruple Combination:

106I, 248D, 275Y, 286S

The following permutations are now represented on the nine 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

Until the 2009-08-21 deposit of the two Washington sequences, all 275Y TamiFlu-Resistant specimens on PF11 backgrounds were paired with 106I. Today we see 3 of 9 with 106V.

The addition of Singapore57 re-leverages position 248 to Aspartate (D) with 5 specimens versus 4 with Asparagine (N). No TamiFlu Resistant specimen on file displays 286G as yet.

Many TamiFlu Resistant cases have been reported that have not been sequenced and deposited in the United States and worldwide.  Dr. Jonathan McCullers of St. Jude Children's Research Hospital in Tennessee reported a TamiFlu Resistant case yesterday, along with 12 child ICU cases and one child death.  Dr. McCullers indicates "a tremendous rise in cases" which began approximately one week after school resumed, well within the 3-10 day incubation period that we predicted post-congregation.  Dr. McCullers maintains that we are in the beginning of a two year pandemic that will have multiple peaks.  We agree that a period of 13 to 24 months from March 2009 is well within the expected duration.  Considering PF11's current position in the inter-species Influenza Flux and the high genetic variance demonstrated by the Hydra Effect, the lower boundary of our estimate (13 months) is unlikely unless the Case Fatality Rate increases significantly because PF11 rapidly depletes the population of potential hosts.

23 clinical observations have been publically discussed as TamiFlu Resistant in recent weeks around the world and most are not yet sequenced and deposited.  These cases concur with many of the geographic regions having sequences on file that match current TamiFlu Resistant sequences but for the H275Y.  In other words, the genetic acquisitions were predictable and expected to occur upon a proximal donor with 275Y co-infecting a host in that region.  An opportunity to review the full diversity of the anti-viral resistant strains would allow determination if, in fact, a silent spread of human-fit and reasonably transmissible TamiFlu Resistant strains is underway at this time or if we are seeing the improbability of an extensive and accurate selection due to treatment that is currently being purported as an explanation.  Evidence exists tending toward a silent spread, including that a substantial list is described with very early sampling and detection of H275Y, prior to any acceptable period for de novo / selective revision.  A minor sub-population of 275Y may be incorporated widely into the PF11 reservoir at this time.

The two youth in early July attending the North Carolina summer camp either spread their PF11 version one to the other or were each infected from a common carrier with a parental PF11 275Y Neuraminidase as is evidenced by the co-factor SNP on the NA of their sequences coding for 223V, known to amplify the 275Y TamiFlu resistance in H3N2.

A more robust database of sequences would be useful to invigorate the scientific community and the public in navigating this distant journey.

An n higher than 9 may assist us to align.

Please visit GeneWurx.com for insight into the latest published studies.

NA Dual Combination 106I and 248N; 22 PF11 Sequences; 1 in United States

Human-fit Seasonal H1N1 from 2008 and 2009 typically demonstrates the H275Y TamiFlu Resistance marker and a NA Triple Combination at 106, 248 and 286:

106I, 248N, 286G

As of today, GenBank shows only one sequence on file from the United States demonstrating a match to the NA Dual Combination of 106I and 248N and the consensus interior region:

• A/Louisiana/03, sampled on 2009-05-01 from a 1 year old female

Only 22 total sequences worldwide match 106I, 248N and the interior consensus region (146 residues).

• Italy (1: Italy127)
• Russia (2: Ekaterinburg01 & Almati01)
• US (1: Louisiana03)
• Asia (18)
• Japan (15, including TamiFlu Resistant Osaka180)
• China (2: Shanghai71T & Nanjing1)
• Korea (1: Korea01)
  

The US Louisiana03 is an exact amino acid match to Almati01 and all of the Japanese sequences but the Osaka180 (variance 275Y).  Louisiana03 matches the two Chinese sequences exactly at the amino acid level, varies from Ekaterinburg01 by only 259D, varies from Italy127 by only 256L and varies from Korea01 by only 319R.

Europe, North America and Asia are now penetrated with the NA Dual Combination of 106I and 248N in the PF11 reservoir matching 2008 and 2009 H1N1 Seasonal Influenza and laying the groundwork for additional TamiFlu Resistance.

Please visit GeneWurx.com for insight into the latest published studies.

United States (NorthEast) HA Diversity at 206; 296H Intra-Segment Exclusivity Continues

A pair of sequences each from Pennsylvania and Rhode Island deposited at GenBank on 2009-09-10 demonstrate continued Hemagglutinin diversity within single geographies and similar time frames.  Multiple PF11 sub-clades in the United States and worldwide show ongoing human fitness and co-existance ability producing a Hydra Effect.

• A/Pennsylvania/06 (PA06) demonstrates 206S and 296H
• A/Pennsylvania/14 (PA14) demonstrates 206T and 296Q,  218X

• A/Rhode Island/07 (RI07) demonstrates 206S and 296H
• A/Rhode Island/08 (RI08) demonstrates 206T and 296Q

• A/Massachusetts/10 (MA10) demonstrates 206S and 296H
• A/Indiana/17 (IN17) demonstrates 206S and 296H

As of this moment, the Intra-Segment Exclusivity between 296H and 206T continues on the PF11 background.  Pennsylvania, Rhode Island and Massachusetts have observed candidate donors of 206T; however, the genetic diversity of 206S with 296H remains in those states and with similar occassion in many international locales.

The highly correlative 2E is found in the 4 referenced 296H Hemagglutinins in this United States deposit.

PA06, RI07, MA10 and IN17 are an exact nucleotide match to A/Italy/127 from 2009-06-17, the only PF11 sequence in the world to carry the 256L on Neuraminidase (with 106I/248N). 

The rare 256L is originally found on the 1918 Brevig Mission sequence.  256L candidate donors include many H3N2 2008 Seasonal Influenza specimens and several H1N2 2008 swine from Oklahoma and Texas.

RI07 on Segment 6 (Neuraminidase) is an exact nucleotide match to a pivotal sequence that will be detailed later from Germany, A/Bayern/66.  The IN17 NA also tracks to RI07 and Bayern66 at 1409 of 1410 nucleotide positions.  Bayern66 is strongly related to the HA of the Russian and Northern European heralds of HA:226R, Omsk01, Ekaterinburg01 and Finland553 and to the HA of Tomsk01.

Please visit GeneWurx.com for insight into the latest published studies.

HA:200T matching High-CFR H5N1 Gharbiyah emerges in Taiwan. HA instability expands

The 80% CFR Gharbiyah, Egypt H5N1 cluster carries HA:200T.  This polymorphism has increased its PF11 range with an entry into Taiwan and is now found in 10 sequences on the pandemic background:

• Taiwan (June) A/Taiwan/115
• United States, East and West Coast (4 in April)
• Japan (4 in June)
• Italy, Milan (May)

Taiwan115 also shows HA:414I which is found on 19 other PF11 sequences (some duplicates) ranging into the Eastern US (8), Australia (4), China (4), Germany (2) and Canada(1).

Another position of interest continues with Genetic Acquisition activity into Taiwan.  286E is found on A/Taiwan/126 and one US specimen, NY3629, a total of 2 PF11 instances.  No point of Ultimate Origin is yet established at this time for 286E; however, instability exists at this amino acid position throughout the H1N1 and H5N1 serotypes.  At least 6 values are on file at 286 within our reservoirs of interest (Donor Candidate serotypes).

286K:  PF11 Consensus
286E:  Taiwan126, NY3629
286H:  1918 (3), IowaSwine1930
286L:   Lab_Virulent_hvPR8_34
286M:  H5N1 Viet human (2) and Hunan Chicken
286Q:  Seasonal H1N1 2008, 2009, WSN33 and KoreaSwineS175

Continued H1 (Hemagglutinin) high variability is expected due to 286 instability and geographic spread of 200T and 414I.

Please visit GeneWurx.com for insight into the latest published studies.

Washington29 PB2 Virulence Factor Domain, Mixed Signal at residue 703 Matches Shanghai71T from May

Segment 1 (PB2) of the previously deposited TamiFlu Resistant Washington29 specimen was entered this evening at GenBank with a mixed signal at residue 703, downstream from a recognised Virulence Factor at 701.

We have seen movement at those residues within ΣPF11^* previously in a very important Chinese sequence.  The May 31 version of A/Shanghai/71T carried the following PF11 PB2 Polymorphisms including Virulence Factors¹.

• E627K
• D678N
• D680N
• D701N
• R703K

Considerable laboratory effort continued with this Chinese specimen due to the Trait-Enhancing nature of the E627K genetic acquisition.  The first Shanghai71T sub-clone also carried E627K; whereas, the second sub-clonal version published on 2009-06-24 of Shanghai71T reversed all but the 703K.

We have also noted variance within ΣPF11 and potential donor candidates in the adjacent upstream area to the Palese lab's PB2 Virulence Domain.  Movement at residues coding for amino acids 674T and 677G are noted in particular and may require additional study to determine trait correlation. 

674T features on a Hong Kong swine (HKswNS1659), a lab virulent Puerto Rico8 variant (LabVir_hvPF8), the last two previous Seasonal H1N1 reservoirs and is found in conjunction with 627K, the Seasonal NA Quadruple Combination (106I, 248N, 275Y, 286G) and TamiFlu Resistance on the 2009 H1N1 Seasonal specimen A/Shanghai/LWS1.  677G is found on the PF11 background throughout Europe and the US Eastern seaboard, but more importantly is in conjunction with 627K on 2006 and 2007 Indonesian H5N1 specimens.

The TamiFlu Resistant Washington29 sequence in the United States acquiring PB2 material in and around this recognised PB2 Virulence Domain begins to build a formidable virus.

1. Steel J, Lowen AC, Mubareka S, Palese P (2009) Transmission of Influenza Virus in a Mammalian Host Is Increased by PB2 Amino Acids 627K or 627E/701N. PLoS Pathog 5(1): e1000252. doi:10.1371/journal.ppat.1000252

Please visit GeneWurx.com for insight into the latest published studies.

TamiFlu Resistance in Texas with no sample date, NA:H275Y

The NA and HA for A/Texas/47 was deposited today at GenBank with no sample date, host age or clinical notes and is a close amino acid match to the Washington28 resistant sequence.

The NA of TX47 is an exact nucleotide match at all positions (1409) but C823T (TamiFlu Resistance) with Nanjing02, Pennsylvania10, Illinois04 and Arkansas03.

TamiFlu Resistance is indicated via 275Y on the Neuraminidase.  The sequence displays the following NA Quadruple Combination:

106V, 248N, 275Y, 286S

The following permutations are now represented on the eight 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
 
Until the 2009-08-21 deposit of the two Washington sequences, all 275Y TamiFlu-Resistant specimens on PF11 backgrounds were paired with 106I.  Today we see 3 of 8 with 106V.
 
The trending toward a stronger pairing of 248N with 275Y continues as discussed in the Washington Post with a 50 / 50 split of the specimens carrying Asparagine (N) and Aspartate (D). 
 
The Hydra Effect will be more strongly documented when the population size of the sequence database increases. 

An n equal to 8 gives little to contemplate.

Please visit GeneWurx.com for insight into the latest published studies.

HA:237I Downstream from RBD in TaiwanT1821 and 4 Russian Specimens

A rare Isoleucine, 237I, occurs within ΣPF11 downstream from the Receptor Binding Domain in A/Taiwan/T1821 sampled 2009-05-30 and in 4 Russian sequences.  206T is shared in all five 237I sequences.

Three of the four Russian sequences are from Moscow and were sampled on 2009-05-26 in the same week as the Taiwan sequence.  The fourth is Irkutsk02 that also carries the RBD polymorphism 226R.

An intra-segment exclusivity exists between 206S and 237I at this time upon PF11 backgrounds.

Please visit GeneWurx.com for insight into the latest published studies.

Italy HA Homology to two TamiFlu-Resistant Asian Specimens

• A/Italy/130, sampled 2009-06-10 from a 43M

Italy130 is an exact nucleotide match on segment 4 (Hemagglutinin/H1) with the TamiFlu-Resistant A/Hunan/SWL3 from China, with 21 North American sequences and with 1 sequence from Sao Paulo, Brasil.  Furthermore, Italy130 is a 1700/1701 nucleotide match to TamiFlu-Resistant A/Yamaguchi/22 from Japan.

No segment 6 (Neuraminidase/N1) is published  for any of the 6 Italian sequences released today, including Italy130; ergo, TamiFlu-Resistance cannot be invalidated by data. 

Absence of data is apparently being commissioned as the new art form?

Please visit GeneWurx.com for insight into the latest published studies.

Taiwan Deposits 3 Sequences Today: 206T found in 7 of 8 Taiwan Samples on File, 296H in the 8th.

Taiwan has 8 PF11 sequences on file at GenBank from mid-May to June 2009 across a somewhat representative sample of host ages (5, 19, 22, 24, 27, 32, 32 and 52).

The 3 new sequences today, sampled in June, continue the local trend of 206T conservation on Hemagglutinin. 7 of the 8 Taiwan sequences on file carry the Threonine at 206.

Of special interest is the 8th sequence, A/Taiwan/T1773, submitted on 2009-08-10 from a 19F sampled in late May showing 206S and the only 296H in Taiwan, demonstrating again the intra-segment exclusivity of 296H and 206T. Though geographic and timing consensus is 206T in Taiwan, the 206S in the 19F appears with the 296H.

TaiwanT1773 also demonstrates the strong pairing between 296H and the 2E originally found in 1918 sequences and now several PF11 HA segments.

The TaiwanT1773 sequence matches Finland555 and its 19 equal worldwide sequences (NE US, Italy and Brasil) but for the disquieting combination SNP and downstream adjacent deletion near the tail of the HA. Furthermore, the TaiwanT1773 sequence is distinct at a different position from each of other regional 296H carriers, e.g. Shanghai143T, Tokushima1, and Shandong1.

Please visit GeneWurx.com for insight into the latest published studies.

Toronto Adds 2 Sequences to NA Triple Combination Analysis with 286G

Toronto sequences filed at GenBank today add numbers 29 and 30 to ΣPF11 for 286G on Neuraminidase .  The bulk of the PF11 286G sequences cluster in Catalonia, but these two sequences from Toronto augment a NA Triple Combination occurring in Canada.  Canada and Catalonia are the only regions of the world currently reporting this PF11 coding that is also found in 1918 sequences, the high-CFR H5N1 Gharbiyah, Egypt specimens and is common in Seasonal Influenza from 2006, 2007 and 2008.

• A/Toronto/T5294/2009 (TorT5294) collected on 2009-05-30 from 22F
• A/Toronto/C0270/2009 (TorC0270) collected on 2009-05-24 from 33M

These two new Toronto specimens and the other four original Canadian sequences carrying 286G also code for 106V and 248N matching the two TamiFlu resistant sequences from Washington at 106 and 248.

Human-fit Seasonal H1N1 from 2008 and 2009 typically demonstrates the H275Y TamiFlu Resistance marker and a NA Triple Combination at 106, 248 and 286:

106I, 248N, 286G

These two sequences from Toronto in May 2009 follow the worldwide pattern exhibiting a particular permutation of the NA Triple Combination:

106V, 248N, 286G

The two sequences parallel the previously discussed TorontoT5308 sequence with the exception of TorT5294 also showing 382A.

Of the 30 sequences on file bearing 286G, all but Catalonia397 bear 248N and all 30 show 106V.  An intra-segment exclusivity on NA exists presently in PF11 between 106I and 286G though 106I donors are proximal in Catalonia and Canada.

Are we seeing enhanced conservation within a PF11 sub-clade being primed for TamiFlu Resistance?

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NA 106V and 248D in April 2009 Toronto Sequence Released Today, Distinct

A/Toronto/3184, sampled in April 2009, now becomes the ultimate origin on file for the Northern Hemisphere for the previously discussed 4th permutation of the NA Dual Combination at amino acid positions 106 and 248.

This early PF11 sequence demonstrates 106V and 248D and appears distinct from the April 2009, A/Auckland/4, and the A/Toronto/R8564 specimen sampled in July that are the only other sequences in the PF11 reservoir on file with these two amino acid codings.  The Toronto3184 NA is most similar (1422/1423) to a series from Stockholm, Zhejiang2 and Finland555 (all 106I).

The NA Dual Combination of 106V and 248D is found 3 times: New Zealand and Canada (April) and Canada (July).

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296H on Hemagglutinin in Young Victims Continues to Broaden into Canada

A/Toronto/T9842 sampled on 2009-06-17 from a 9 year old and A/Toronto/T5362 sampled 2009-06-09 from a 14 year old demonstrate the Genetic Acquisition of 296H.

As of this time in the PF11 reservoir, the rare 296H (in less than 40 specimens) remains exclusive of 206T.

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Toronto re-emergence of 4th PF11 Neuraminidase Permutation at positions 106 and 248

A/Toronto/R8564, sampled 2009-07-06, rescues the 4th permutation of the NA Dual Combination at amino acid positions 106 and 248.  The PF11 sequence demonstrates 106V and 248D, a combination that was previously found only once within ΣPF11, early in the pandemic in April 2009, A/Auckland/4. 

This re-emergence of the permutation returns a 4th version of the NA Dual Combination to activity on PF11.

The TorontoR8564 NA is an exact amino acid match to the Auckland4 sequence from April.  The certain interchange that occurs between the two cities on a regular basis would lead us to investigate for re-assortment potential.  However, re-assortment is impeached from this investigation due to the 2 polymorphisms at the nucleotide level:

Several Auckland sequences carry the G76A.

G355A is found in only 14 worldwide ΣPF11 strains:  Toronto, China, Japan, Spain, Australia and 5 in the Southern United States.

The N1 backgrounds are widening in a fashion suggestive of non-random genetic acquisition with this completion of the permutation set concerning the NA Dual Combination at positions 106 and 248.

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Hemagglutinin of NewYork4014 (2009-06-10) is exact match to Tokushima1 (2009-06-02) with 145I and 296H.

A sequence from Broome County, New York deposited today at GenBank, A/New York/4014, is an exact match on the Hemagglutinin to the Japanese sequence, A/Tokushima/1.  NY4014 was sampled 8 days after the Japanese sequence.

These two sequences are also an exact HA match to a previous NY sequence, A/New York/3573, taken 2009-05-21.

The NY4014 and Tokushima1 homology fails on other gene segments as the NY4014 appears relatively stable to the PB2, NA and NS1 segments' PF11 consensus. The NY4014 NS1 is an exact match to NY3573.

Of particular note on the NY4014, Tokushima1 and NY3573 HA segments is the 145I that sets apart only 6 sequences within ΣPF11:

As you can see from the table, the most current samples with 145I carry 296H, a polymorphism of interest on HA.

The intra-segment exclusivity trend between 296H and 206T continues to exist within ΣPF11.

A NY-Japan-NY segment transfer is not surprising given international air travel.  A more robust database would allow greater acuity into the interpretation of the ultimate origin of this rare HA event.

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