2014-01-02

Novel London pH1N1 2013 Case Displays Promiscuous Genetics

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 Excel for completeness in citation.

Publish Date : 2014-01-02
Last Update : 2014-01-03
1 Sequence

On 2014-01-02, the Health Protection Agency of the United Kingdom released a pH1N1 sequence with a GISAID submission date of 2013-12-30 that was sampled in London during November of 2013.  No age, gender, patient status, vaccination status or outbreak metadata was provided.

On this same day, the Guardian news outlet asserted to no small response that the UK was not prepared for a flu epidemic.  These reporters may be more accurate than they realise, but for an altogether different reason than they have developed in the filing.

UK 'unprepared for flu epidemic'
Changes to NHS mean country will be unable to cope with major outbreak of disease, possibly leading to thousands of deaths
Denis Campbell, health correspondent
The Guardian, Thursday 2 January 2014 15.01 EST
'The Cabinet Office has advised local resilience forums to lay plans to tackle a potential pandemic that could affect up to half the population, lead to as many as 4% of those affected being admitted to hospital, and cause "excess deaths in the range of 210,000-315,000 nationally".'

The UKEnglandLondon624_2013_11_04 sequence is novel at the Hemagglutinin segment and at the Neuraminidase segment.  More importantly, the sequence background is very permissive to acquisition of avian influenza genetics, but acquisition may not be required for similar cases to become severe.

In the past 11 months, homologous backgrounds have regularly demonstrated a capacity for raising a minority quasi-species of HA 225G and / or HA 194I in certain individuals to a dominant population.  Those Receptor Binding Site polymorphisms are documented to produce deep lung involvement due to a shift in binding preference toward alpha 2,3 galactose receptors.

Expect small clusters with exceptionally poor clinical outcomes should the conditions arise to manifest these HA 225G and 225N genetics.  The compound effect of potential NHS turmoils brings visage of 2009 when patients were air-shipped for ECMO from under-staffed and over-capacity Critical Care Units all over the country.

HA Polymorphisms

. . . . UKEnglandLondon624_2013_11_04 (
. . . . . . . . A/ENG/624/2013
. . . . . . . . H7N9 Correlation HA 116K
. . . . . . . . H7N9 Correlation NA 48A and 321V
. . . . . . . . Host Transition HA 116K
. . . . . . . . Host Transition Potential HA 218E
. . . . . . . . Novel Hemagglutinin
. . . . . . . . Novel Neuraminidase VISA
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI497687
. . . . . . . . GISAID Isolate EPI_ISL_152932
. . . . . . . . 25 Polymorphisms (10 Amino and 15 Silent)
. . . . . . . . syn#4Y (TAc),
. . . . . . . . syn77S (AGt),
. . . . . . . . 100N,
. . . . . . . . 116K [Emergent H7N9 wild type],
. . . . . . . . . . . . [pH1N1 ReEmergent 2013],
. . . . . . . . . . . . [pH1N1 2013 Rare: 4 Cases over 5 Sequences],
. . . . . . . . . . . . [Early pH1N1:
. . . . . . . . . . . . . . . . 2011 Count 01:
. . . . . . . . . . . . . . . . . . . Tunisia1701_45M_2011_02_10
. . . . . . . . . . . . . . . . . . . . . GenBank HA JN037743
. . . . . . . . . . . . . . . . . . . . . . . Escape Variant
. . . . . . . . . . . . . . . . . . . . . . . . . . with HA 117V, 225G & 273A
. . . . . . . . . . . . . . . . . . . . . . . Strong 225G Correlation
. . . . . . . . . . . . . . . . . . . . . . . . . . for related HA segments,
. . . . . . . . . . . . . . . . . . . . . . . Strong 225N Correlation
. . . . . . . . . . . . . . . . . . . . . . . . . . for related HA segments,
. . . . . . . . . . . . . . . . 2010 Count 05,
. . . . . . . . . . . . . . . . 2009 Count 37:
. . . . . . . . . . . . . . . . . . . UK Regional Marker,
. . . . . . . . . . . . [H7N7 wild type],
. . . . . . . . syn141H (CAc) [H5N1],
. . . . . . . . . . . . . . . . . . [avH1N1farm],
. . . . . . . . 166Q,
. . . . . . . . syn176V (GTt),
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . 218E [H7N7 Host Switching:
. . . . . . . . . . . . . . . . Sea Mammal,
. . . . . . . . . . . . . . . . Commercial Poultry],
. . . . . . . . 259T [pH1N1 Upsilon US Military],
. . . . . . . . 286E,
. . . . . . . . syn308K (AAg),
. . . . . . . . syn325P (CCa),
. . . . . . . . syn333F (TTc),
. . . . . . . . syn338G (GGc),
. . . . . . . . syn372Q (CAa),
. . . . . . . . 377K,
. . . . . . . . syn396V (GTg),
. . . . . . . . syn429L (cTG),
. . . . . . . . syn431L (tTA),
. . . . . . . . syn448L (TTg),
. . . . . . . . 454N,
. . . . . . . . 502K,
. . . . . . . . syn537S (AGc))

NA Polymorphisms

. . . . UKEnglandLondon624_2013_11_04 (
. . . . . . . . A/ENG/624/2013
. . . . . . . . H7N9 Correlation HA 116K
. . . . . . . . H7N9 Correlation NA 48A and 321V
. . . . . . . . Host Transition HA 116K
. . . . . . . . Host Transition Potential HA 218E
. . . . . . . . Novel Hemagglutinin
. . . . . . . . Novel Neuraminidase VISA
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID NA EPI497688
. . . . . . . . GISAID Isolate EPI_ISL_152932
. . . . . . . . 17 Polymorphisms (10 Amino and 7 Silent)
. . . . . . . . 34V,
. . . . . . . . 40I [pH1N1 with NA 247N TamiFlu Resistance],
. . . . . . . . . . .[avH1N1farm],
. . . . . . . . 44S [pH1N1 Upsilon],
. . . . . . . . 48A [H7N9 Avian],
. . . . . . . . 106V [pH1N1 Upsilon],
. . . . . . . . syn125S (TCa) [avH1N1farm],
. . . . . . . . 200S,
. . . . . . . . syn209N (AAt) [pH1N1 Upsilon],
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . syn295N (AAt) [pH1N1 with NA 247N TamiFlu Resistance],
. . . . . . . . . . . . . . . . . . [H9N2],
. . . . . . . . . . . . . . . . . . [H5N1],
. . . . . . . . . . . . . . . . . . [avH1N1farm],
. . . . . . . . 321V [Emergent H7N9 wild type],
. . . . . . . . . . . . [pH1N1 Upsilon],
. . . . . . . . . . . . [H5N1],
. . . . . . . . . . . . [avH1N1farm],
. . . . . . . . . . . . [H6N1],
. . . . . . . . 369K,
. . . . . . . . syn378N (AAt) [pH1N1 with NA 247N TamiFlu Resistance],
. . . . . . . . . . . . . . . . . . [H5N1],
. . . . . . . . . . . . . . . . . . [avH1N1farm],
. . . . . . . . syn383T (ACt) [avH1N1farm],
. . . . . . . . syn409H (CAc) [H5N1],
. . . . . . . . . . . . . . . . . . [avH1N1farm],
. . . . . . . . 432E [Emergent H7N9 LookAsided wild type])

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pH1N1 Influenza Hemagglutinin & Neuraminidase Segments elucidated at 2014-01-02-16_16_23_059060 by GeneWurx see.PolyDetector v0, Copyright 2007-2014.

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