Zoonotic H9N2 Avian Influenza Further Destabilises Pandemic Genetics

2010-03-31
Is the Pandemic Influenza Reservoir Stable?

If you enjoy counting, even measuring by observation, please continue reading.

But you must realize that the iota, the jot and even the title, will be considered of value in this forthcoming exercise. Some in the science community appear to find the process of discovery by observation just too tedious. If you are of that mindset, please direct your attention to any of the many “Science for Hire” venues where illogical, but comforting, summations are drawn from cleverly manipulated data streams. Science sells today. But we sometimes speculate that science is becoming just another sell-out, an industry pursuing profit over knowledge?

On the other hand, if careful examination, even hard work, is part of your daily lab book, you'll find evidence in this discussion to introspect.

Leading public health officials continue even today to indicate that the pandemic virus is unchanged. Keep that statement in mind as you read this analysis of heavy change activity in the pandemic reservoir, watching closely for the recent branching into genetic areas matching H9N2.

Also keep in mind that even single changes have demonstrated substantial importance.

Ongoing worldwide studies duplicated by independent, geographically dispersed laboratories, including the labs of those noted public health officials, indicate that a single polymorphism may produce a significant outcome within a Pandemic Influenza reservoir. Numerous accounts of important revisions are on record across a vast geography. 225G has produced a Vaccine Escape event in LvivN6, an elevated Case Fatality Rate and a substantial number of severe outcomes. Individual changes between 157 and 159 have also demonstrated “low reactor” status and registered as Vaccine Escape events. 230I entered the H5N1 Gharbiyah cluster in Egypt and the resultant Case Fatality Rate was 80% for that strain, a substantial increase from the accepted H5N1 CFR.

Three separate single genetic changes are well characterised in leading to various forms of Anti-Viral resistance. TamiFlu Resistance has now dispersed widely in a pattern following the rapid spread of resistance in seasonal influenza via the same Single Nucleotide Polymorphism coding for 275Y on the Neuraminidase. Emergent and attractant H1N1 strains (Triple Reassortments again) co-circulating alongside the pandemic reservoir also carry 275Y. H5N1 inclusions increase in the pandemic reservoir with a continuous flow. The PB2 627K is confirmed as leading to increased replication speed in humans and has recently been documented in a second pandemic sequence. As we have maintained from the beginning of this pandemic, TamiFlu Resistance and 627K are foregone conclusions according to our calculations.

Our team noted an increase in Avian inclusions and recently predicted HA 230I for ΣPF11. The polymorphism was documented last week in Wisconsin (US) on a background that does not deter transmission. The geographic area has a notable increase in cross-linked activity. The individual sample, A/Wisconsin/629-D00337, is primed for spread with 2 additional HA markers, 275A (TX, NM, CA and Sweden) and 377K (aggressively emerging). The NA carries 220K, a marker found on one cross-linked sequence from the Ukraine and across a wide US geographic pattern from December 2009 to the most recent 2010 sequences (North Carolina, New Hampshire, Wisconsin and Nebraska). We consider the Wisconsin0337 sample to be an excellent candidate as a universal donor of sorts due to limited polymorphisms and the fact that each revision is currently an emergent change.

H9N2, a "bird flu" serotype, has been recently evaluated for human pandemic potential. By all appearances, the present H9N2 reservoir is not becoming a pandemic virus, but is very much influencing the genetic acquisition cycle of the currently circulating PF11 pandemic virus. Which is worse, another species-jumping serotype entering the fray or a combinational virus with genetics from multiple pandemic potential reservoirs appending onto the current partially-adapted virus? In either case, the Hydra Effect appears to be operating in full force.

Given this information, obvious questions begin to form. If one genetic change may potentiate variant clinical outcomes, drug resistance or Vaccine Escape, what is the potential for multiple changes producing a variant outcome? And if a single genetic change and/or multiple changes are capable of producing large changes in behaviour, should we, in turn, have a very high and accurate level of surveillance on this reservoir? And what should we do with that important information? Should our public health officials speak from a platform of candor and accuracy when carrying out the responsibilities of their trusted positions?

Let’s investigate now if the viral reservoir is, in fact, unchanged?

More than 80% of the Hemagglutinin positions between 188 and 244, including antigenic areas of the RBD, are on record as polymorphic. Many positions rate multiple changes. Tracking these revisions against various baselines has informed our studies over the past year. One particular range of those variations is documented in the trailing data. For the sake of brevity, only one section of the HA gene segment is discussed. The list is certainly not comprehensive.

The positional summary may perhaps be instructive for those who hold the belief that the pandemic reservoir is stable. The report may provide reversing guidance for those who make public statements to the effect that pandemic H1N1 is not changing. Repetition of their “All Clear” social messaging cannot reverse the weight of the actual data. Repetition of an untruth does not create a fact, but that ongoing strategy of repetition is apparently very effective in managing the perception and manipulating the belief of the unsuspecting public.

The viral reservoir backing this present pandemic is far from stable and is actively acquiring new genetics. Current data does not indicate an immediate direction toward stability.

As is the nature with an IDRREAV, the positions reported here will not necessarily be the most important amino acid positions in the future. The reservoir will evade immunity and escape vaccine by heavily self-revising in the near future at key locations between 131 and 182 (emphasis at 155 to 177). Variation will occur with lower penetration at the head of the HA and from 272 downstream approximately 55 positions. Potential is very high that 22I will achieve density in one or more sub-clades. Expect 100N to spread and penetrate initially on sub-clades without the 22I appearances. South American polymorphisms from their fatal mid-pandemic strains of 2009 will recycle into the United States and other Northern Hemisphere nations with substantial thrust in the coming 90 days. Acceleration of the Avian based cross-linking will continue in the Western world.

Bear in mind also that a solid portion of the changes documented in this current list will become fixed even as additional donations are accumulated. The zoonotic movement from birds into human PF11 sequences is earnestly progressing in the most recent 45 days of available data. Several polymorphisms, HA and NA, from the Georgia hospitalization resurgence may have originated in Avian Influenza samples. Expect continued acquisition from Avian H5N1 and H1N1, and also watch the acceleration from one particularly new Avian donor serotype. H9N2 demonstrated a human jump in late 2008 and has very recently become fully engaged in ΣPF11 genetics with a well-defined etching on the newest cross-linked sequences. The reservoir flux will also be influenced by Swine H1N2 and H1N1 (emphasis on 3 particular emergent strains).

Is the Pandemic Influenza Reservoir Stable?

You decide . . .

188N SC16, SC31, NY3502, MA15, CatS1187, Milan433, Japan, S5
188I Growing in US on cross-linked background (4), BZSP53823
189V Sydney2503
189T Growing on US cross-linkage (4), H5N1 2009, H9N2 2008
189A synonymous (GCc), Georgia01_2010, swOR4060
190D synonymous (GAt) Milan326, 1918
190Y SwedenMalmoe1_2010_01_01
191R Chengdu18 (129P)
192Q synonymous (CAg) RomaISS50, Nebraska01_2010
193S synonymous (AGc) SC18, US 2010 (3), Milan294, Japan, H9N2
193G AR08
193N Washington72, H9N2
194I NC38E3, VA27, SC18, Bangladesh3009, StPete59, StPete99
194L synonymous (CTa) Japan4081
196Q synonymous (CAa) Wisc (3), Malaysia (2), Milan326
197T Malaysia4039
198V Malaysia5283, Malaysia9117
199N Milan80, Milan83
199D synonymous (GAc) swine Illinois, H5, H9N2
200T FL31, Asia (13), MilanUSHR1, H5, H9N2
200S NC57, SC46
201H Wisc1140, Darwin2140
202A MXinDRE797 2010 TmX, IA14, KY25, HK34360
202V synonymous (GTc) YAMAGATA778, YAMAGATA803, swIllinois
204V synonymous (GTa) PA31, SHIZUOKA1573, 1918, S7
205G synonymous (GGa) Texas76C2, S5, H9N2 (GCa)
206A CatS1161
206T Extensive
207S synonymous (TCg) California01_2010
208K US, UK, HK, MX, Italy (2), Australia (12), Asia (3), swOR4060
208S Australia43, Australia45, ChukkarH6N1
208G NY6292
208T Norway3440
210S synonymous (AGt) Bogota0466N, Malaysia9131, H9N2 (Aat)
210N Texas76C2
211K synonymous MXinDRE50617 (225G)
211R swOR4060_2009_12_31, 1918
212R swOR4060_2009_12_31, 1918
212E Vlad01 (225G), Argentina8574_41, IN21, Malaysia4039
212N MA15
212T Anadyr177_F (225G), CA07X179, CA07X181
213L TX15
213F synonymous StPete99 (225E)
214E Kurgan01, Moldova (3), swOR4060_2009_12_31
214N ENG92960012, SHIZUOKA1514
214Q Wisc0936 (237L)
214K synonymous (AAa) CatS1937, NM13, ENG620, China22811
215P synonymous (CCa) SC33, Eng616, GuangdongyunchengSWL51
215P synonymous (CCt) NY_WC37RG, MO02
216E synonymous (GAg) Moldova (4), Belarus, Bosnia (3, 225G), Indiana, H9N2 (GTg), tn
218A synonymous (GCg) Belarus, H9N2 (GGg)
218E Texas77 (159S, syn173G, 275A, 377K, 454I)
218T Hiroshima201 (225G)
218V GuangdongyunchengSWL51, Malaysia (2 mix wt) (GtA)
218V swIll02930, 2931, 2932, 2937 (2009-12-29, 30) (GTc)
219I synonymous Ancona451_F, Lyon2490
219T Wisc0134 (225E), RomaISS223, swOR4060_2009_12_31
220R synonymous (AGg) Mexico476, Malaysia9451
223V synonymous (GTa) Utah59
223M CA33
224K SC18_VxX
224M NY5186
225N BZ_SP53838, Ukraine mix wt, Victoria2125, Malaysia8860 et al
225E Extensive on multiple backgrounds
225G LvivN6_VxX with syn413K, UkDnip273 (GgT mix wt), H9N2
225G RomaISS1897 & 1941, EgyptVacsera138 (300S) ex225E (Gga)
225E+226R Russia (3), GermanyBY74, swMX4
226R Trabzon01 (Turkey), et al
227A swOR4060_2009_12_31, 1918
227V RomaISS50
227G Utah20 with wt mix
229R synonymous (AGg) swMX04 (225G, 226R)
230I Wisc0337_2009_12_15, H5 Gharbiyah 80% CFR, H9N2
231D Ankara05, OSAKA2143, H9N2 2008
231N CalifVRDL36
231K Wisc0853, Wisc1915, Wisc2337
232Y synonymous (TAc) Florida30, PuertoRico51, H9N2, H5, S9, S7, M7, Sask
233Y synonymous (TAt) AthensINS85, Hiroshima645, H9N2 2008
233H NC Duke (5, wt, 225G, 225N), AZ17 & Australia6
235A CatNS7632, CalifVRDL55
236V Eng93120020, ENG645, H9N2
237I Cal_SDINS69, England (2), Russia (4), Asia (2)
237L Wisc0936 (214Q), 1918, H5, tn
237V synonymous (GTg) Pennsylvania31, H9N2 (TTg), M7 (CTg)
238D Kaliningrad01 (225E+226R), tn
238K Wisc2485 (225E), Spain (2), China, swOR4060, H5, H9N2 2008
238E synonymous. Extensive and recently growing
239P synonymous (CCt) ENG621, swOR4060_2009_12_31
239P synonymous (CCa) Ancona508PG, Russia180, Australia60
240G synonymous (GGg) DC_INS24, H9N2, S9, S7, M7, Sask
241D synonymous (GAt) CatS1943, tn
241G NH17, ENG93040048
241E China22811
242K synonymous (AAg) swOR4060_2009_12_31
244I ThaiCU_H9
244T synonymous (ACt) CatS1935, CatS2120

The truth is in the sequences.

via email from NS1 -


Our analyses are intended to provide the most straightforward explanation possible . . . but as you must realise, the backing science of Influenza is far from robust. Simplicity is simply not attainable. Though the community produces thousands of point studies with valuable content data, a lack of cohesive framework results in frequent knowledge gaps. We are working to bridge those gaps, but today’s tools and the scarcity of data unfortunately limit the scope.

H5N1 and H9N2 are the two Influenza A serotypes considered most capable of reaching human pandemic status. Each is on record as zoonotic. H5N1 has been an active, but limited, contributor to ΣPF11. Throughout the current human pandemic, H9N2 has provided consistent influence as well. In the most recent sequences, a new trend is emerging as H9N2 accelerates to become a dominant contributor, especially on the cross-linked backgrounds.

If you’re able to review the idea of Influenza Flux at GeneWurx.com, you’ll begin to understand why an emergent contributor (H9N2) to a presently adapting viral reservoir is important. Every new combination presents the human immune system with a potentially separate challenge. An advancing Avian Influenza donor reservoir introduces new genetic material that is quite valuable to the virus, but quite dangerous to humans. Until the pandemic viral reservoir reaches a level of stability, an Omega state, the clinical outcomes may be highly variant with symptoms and outcomes that are beyond the normal parameters of seasonal influenza.

In a word, the pandemic virus is “confused”.

That’s what a pandemic is: a virus that doesn’t belong in humans, but really wants to belong. And, as you’ve seen, a pandemic reservoir is willing to do some work to become capable. This reservoir will continue to produce “confused” symptoms and “confused” outcomes until some reasonable stasis is achieved with the human host.

Yes, advancing H9N2 influence will be more of a problem. An accelerating donor pool from an Avian Influenza serotype is more likely than not to prolong the adjustment period.