2010-09-27

225G Sequence from Pennsylvania Extends Sub-Clade with Fatality Markers from Russia and Brasil

Last Updated 2011-03-29

January to August 2010 Expansion of One Hydra

On 2010-08-07 and the following weeks, GeneWurx discussed the spread of one remarkable Hydra across the US, Germany and the Ukraine.  HA 230I is represented in this sub-clade on a sequence from the US state of Minnesota.  HA 225G (GgT) now enters this sub-clade in the US state of Pennsylvania.  The sub-clade appears to be one of several that are permissive to a combination of 225G (GgT) and 230I within post-pandemic H1N1.

On 2010-09-24, the US CDC released a set of sequences at GISAID that included six from the United States.  Pennsylvania07_2010_08_12 was sampled from a 24 year old female.  No clinical information is provided, nor outcome. 

The sequence carries 13 polymorphisms on the HA alone and typifies the rapid genetic acquisition that continues on the most current samples in the United States.  Six of those changes place the sequence with 11 other cases across the United States, the Ukraine and Germany.

Follow 6 HA polymorphisms (3 silent) tracing onto this 12th sequence through the 8th distinct geographic location:

34D, 165N, 189T, syn213F, syn305K, syn346G.

Five of the six polymorphisms are found in animal influenza reservoirs (zoonotic) and the sixth shares nucleotide homology with recognised zoonotic reservoirs.  Is this another strain linking the US to flu strains from the Ukraine, India or Russia?

. . . . Pennsylvania07_2010_08_12 (
. . . . . . . . 34D,
. . . . . . . . syn118E,
. . . . . . . . 140T,
. . . . . . . . 165N,
. . . . . . . . 189T,
. . . . . . . . syn213F,
. . . . . . . . 225G (GgT),
. . . . . . . . 275I,
. . . . . . . . syn287G,
. . . . . . . . syn305K,
. . . . . . . . syn329S,
. . . . . . . . syn346G,
. . . . . . . . 451E [Unique to Japan])

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.

Previous Study on this Topic:



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2010-09-26

HA 230I RBS Polymorphism Potential for Pennsylvania

Current trending indicates a reportable potential for the M230I polymorphism spreading on the Hemagglutinin of PF11. This Receptor Binding Domain change may enhance Vaccine Escape from the currently selected vaccine target candidate, CA/07 X181. 

For those who are following the prediction on February 25, 2010, the pandemic reservoir now shows multiple instances of multiple encodings for 230I.  Model adjustment and data transparency allowed a second set of detailed geographic predictions on 2010-08-09 that have also found traction.

The 230I bearing sequences meeting the prediction are documented in the detailed discussion on Vaccine Escape that demonstrates a 100% change rate in the pandemic influenza (pH1N1) reservoir at the critical HA genetics range between amino acid positions 186 and 248.  89% of the amino acid positions have notated revisions.

Expectations for the M230I polymorphism, that first came to our notice for zoonotic concern on the H5N1 human fatality cluster, have now been revised based on the most current public data.  The GeneWurx model approximates that HA 230I will appear in the PF11 RBS according to the following geographic probabilities.

  • 45% probability in Pennsylvania sampled by 2011-01-01.
These probabilities will be updated as additional data is made public.  Transparency at this post-pandemic stage is essential to formulate viable responses for the risk groups.  Release of sequences and clinical data of a finer detail and higher quantity will allow information-based decisions.


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2010-09-24

Pandemic Influenza and Avian Influenza Conjunctivitis Presentation

Last Updated 2010-09-30

Large outbreaks of eye inflammation (conjunctivitis), including hemorrhagic conjunctivitis, have begun around the world this month with several regions registering case counts in the thousands.  Viral infection is frequently associated with this type of highly contagious "Pink Eye" or "Red Eye".  Early pandemic H1N1 cases document these types of eye redness in the patient symptomology.


One recent HA polymorphism found in the pandemic reservoir has been previously associated with viral conjunctivitis with and without classic influenza symptoms. The amino acid value of HA 188T is strongly correlated to conjunctivitis on the Netherlands human H7N7 outbreak during 2003, including zoonoses from commercial poultry operatons. One human fatality was recorded during that outbreak and that case sequence shows the HA 188T.
The 6 pH1N1 sequences that carry 188T (all recent) also demonstrate a significant set of markers with homology to zoonotic serotypes including further H7N7 amino acid homology and extensive H7N7 SNP potential. H9N2 and H3N8 also are potential contributors, but the data sparsity inclines our team to be more concerned with an H7N7 / H9N2 team coordination from commercial domestic poultry operations.

Avian influenza again may be communicating with the human pandemic H1N1 Hydrae. India today, 2010-09-30, is on record in a section of Mumbai as counting 2,500 cases of conjunctivitis this month.  HA 188T is also found in India.

. . . . Florida14_24M_2010_08_05 (
. . . . . . . . 100N [H7N3, H7N7, H9N2],
. . . . . . . . syn161Y [H3N8 2009, H6N1, H9N2],
. . . . . . . . 188T [H6N1, H7N7],
. . . . . . . . syn338G [H3N8, H4, H5, H6, sw],
. . . . . . . . 377K [H9N2],
. . . . . . . . 442I mix,
. . . . . . . . 454N [H7N3, H7N7, H9N2])

. . . . OZVictoria512_2010_07_30 (
. . . . . . . . syn60I,
. . . . . . . . 100N [H7N3, H7N7, H9N2],
. . . . . . . . 188T [H6N1, H7N7],
. . . . . . . . syn285P,
. . . . . . . . syn338G [H3N8, H4, H5, H6, sw],
. . . . . . . . 377K [H9N2],
. . . . . . . . 454N [H7N3, H7N7, H9N2])

. . . . Thailand34_9912_2010_07_14 (
. . . . . . . . 188T [H6N1, H7N7],
. . . . . . . . 200T,
. . . . . . . . HA truncated after aa253)

. . . . Thailand34_9937_2010_07_14 (
. . . . . . . . 162Q [Unique to PF11 GenBank/GISAID],
. . . . . . . . 188T [H6N1, H7N7],
. . . . . . . . HA truncated after aa253)

. . . . NZChristchurch15_2010_07_12 (
. . . . . . . . 100N,
. . . . . . . . 188T [H6N1, H7N7],
. . . . . . . . syn338G [H3N8, H4, H5, H6, sw],
. . . . . . . . 377K [H9N2],
. . . . . . . . 454N [H7N3, H7N7, H9N2])

 . . . . India5107_2010_06_28 (
. . . . . . . . syn60I,
. . . . . . . . 100N [H7N3, H7N7, H9N2],
. . . . . . . . syn135V,
. . . . . . . . 188T [H6N1, H7N7],
. . . . . . . . syn338G [H3N8, H4, H5, H6, sw],
. . . . . . . . 377K [H9N2],
. . . . . . . . 454N [H7N3, H7N7, H9N2])

. . . . India8910_2010_05_08 (
. . . . . . . . syn49G [H7N3, H7N7],
. . . . . . . . syn51A,
. . . . . . . . 188T [H6N1, H7N7],
. . . . . . . . syn338G [H3N8, H4, H5, H6, sw],
. . . . . . . . 377K [H9N2],
. . . . . . . . 454N [H7N3, H7N7, H9N2])

. . . . swThaiCURA75_2010_01 (
. . . . . . . . 188T [H6N1, H7N7],
. . . . . . . . 263D,
. . . . . . . . syn350G [H7N3, H7N7],
. . . . . . . . 414I,
. . . . . . . . syn484N [H3N8, H4, H5N1 (E/A/H), H6, H7N7, H9N2, H11])

The human post-pandemic reservoir continues to diversify and augment from a wide variety of avian, canine and equine sources. Sampling and sequence confirmation may corroborate that Mexico, China or Pakistan has HA 188T in the PF11 reservoir near the same geographies where the eye symptoms are occurring.




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2010-09-19

Australia Shows Novel HA 238D in August 2010 on Hyper-morphic Sequence

The WHO Collaborating Centre for Reference and Research on Influenza deposited a group of 74 sequences on 2010-09-15 primarily from Australia and New Zealand with 9 from Asia and 2 from Oceania (Fiji and Papua New Guinea).

A nine year old female patient from Little River, Victoria, Australia was sampled by the Monash Medical Centre on 2010-07-24 during the current influenza epidemic. That sequence, OzVictoria508_9F_2010_07_24, is one of only six in this deposit without an antigenic characterisation. The HA gene segment carries 14 polymorphisms.

Significant homology exists with H5N1 and H7N7. Changes at amino acid position 238 and the region are associated with the 230I polymorphism. With the numerous polymorphisms and the lack of antigenic testing, this sequence is suggestive of immune escape tendencies.

The continual building of changes onto the pandemic H1N1 background requires ongoing surveillance.  Genetic data continues to ebb from Asia, India and Oceania into Fall European and North American sequences.  India is represented in the conforming predecessor polymorphism list for this Australian sequence.  Finding similar genetic quality in the near future is a reasonable expectation for the upcoming North American epidemic.

. . . . OzVictoria508_9F_2010_07_24 (
. . . . . . . . 35I [H5N1],
. . . . . . . . 88P [H2N3, H5N1, H11],
. . . . . . . . . . . [HunanHechengSWL1616_2009-11-23,
. . . . . . . . . . . KoreaAF2376_2009_10_27
. . . . . . . . . . . . . . . with 280A and 290K
. . . . . . . . . . . Nevada15_9F_2009_09_10
. . . . . . . . . . . . . . . with 22I, 225E, 256F, 299Y,
. . . . . . . . . . . . . . . . . . 299Y, 300S, syn384S,
. . . . . . . . . . . GermanyCologne13_2009_06_29
. . . . . . . . . . . . . . . with 35I, 38V, syn108L,
. . . . . . . . . . . . . . . . . . syn205G, 206s, syn276H],
. . . . . . . . syn102E [SingON2407_2009_12_13,
. . . . . . . . . . . . . . . Singapore544_2009_12_10,
. . . . . . . . . . . . . . . Brussels243_2009_11_09
. . . . . . . . . . . . . . . . . . . . with syn44L and 89G],
. . . . . . . . syn152I [CalifVRDL115_2009_12_04,
. . . . . . . . . . . . . . . NY6939_2009_12_11,
. . . . . . . . . . . . . . . tkOntarioFAV117_1C_2009_12_07
. . . . . . . . . . . . . . . . . . . . with 35I, syn219I, syn276H,
. . . . . . . . . . . . . . . . . . . . . . . syn456L, 463V, 523A,
. . . . . . . . . . . . . . . England1050_2009_12,
. . . . . . . . . . . . . . . Scotland103_2009_12,
. . . . . . . . . . . . . . . England1051_2009_12,
. . . . . . . . . . . . . . . ItalyAncona451_2009_11_27_f,
. . . . . . . . . . . . . . . NY6607_2009_11_24,
. . . . . . . . . . . . . . . CalifVRDL107_2009_11_15,
. . . . . . . . . . . . . . . CalifVRDL101_2009_11_05,
. . . . . . . . . . . . . . . DC_114_2009_11_04,
. . . . . . . . . . . . . . . England94800096_2009_11,
. . . . . . . . . . . . . . . Calif_SD35_2009_10_26,
. . . . . . . . . . . . . . . NY5447_2009_10_23,
. . . . . . . . . . . . . . . CalifVRDL84_2009_10_09,
. . . . . . . . . . . . . . . CalifVRDL87_2009_10_09,
. . . . . . . . . . . . . . . IndiaPune6196_2009_08,
. . . . . . . . . . . . . . . IndiaDhule9433_2009_08,
. . . . . . . . . . . . . . . SantoDomingoWR1057N_2009_07_02,
. . . . . . . . . . . . . . . SantoDomingoWR1058N_2009_07_02,
. . . . . . . . . . . . . . . SantoDomingoWR1059N_2009_06_30],
. . . . . . . . 206S,
. . . . . . . . syn219I [CalifVRDL115_2009_12_04
. . . . . . . . . . . . . . . . . with 35I, syn152I, syn276H,
. . . . . . . . . . . . . . . . . . . . syn456L, 463V, 523A,
. . . . . . . . . . . . . . FL_Pen213_2009_11_17
. . . . . . . . . . . . . . . . . . . . with 35I, syn152I, 273A,
. . . . . . . . . . . . . . . . . . . . syn456L, 463V, 523A,
. . . . . . . . . . . . . . CalifVRDL107_2009_11_15
. . . . . . . . . . . . . . . . . . . . with 35I, syn152I, syn276H,
. . . . . . . . . . . . . . . . . . . . syn456L, 463V, 523A,
. . . . . . . . 238D (GAc) [H2N3, H7N3, H7N7],
. . . . . . . . . . . . . . . . . . [Belgorod2_2010-03-15 (GAt),
. . . . . . . . . . . . . . . . . . Kaliningrad01_2009_11_02 (GAt)
. . . . . . . . . . . . . . . . . . . . . . . . with 225E and 226R,
. . . . . . . . . . . . . . . . . . AthensINS398_2010-01-24 GAt),
. . . . . . . . . . . . . . . . . . KaliningradCRIE_DA_2009-09-26 (GAt),
. . . . . . . . . . . . . . . . . . KaliningradCRIE_KG_2009-09-25 (GAt),
. . . . . . . . . . . . . . . . . . KaliningradCRIE_MA_2009-09-25 (GAt),
. . . . . . . . . . . . . . . . . . KaliningradCRIE_SHD_2009-09-25 (GAt),
. . . . . . . . . . . . . . . . . . KaliningradCRIE_ZD_2009-09-25 (GAt)],
. . . . . . . . syn247A [Belize8756_2009_10_08,
. . . . . . . . . . . . . . . Singapore93_2009_06_22]
. . . . . . . . syn254P,
. . . . . . . . 272G [Niigata19_2009_12_31,
. . . . . . . . . . . . GuangdongSWL36_2009_11_29],
. . . . . . . . syn276H [1918, S5],
. . . . . . . . syn388K [H5N1],
. . . . . . . . . . . . . . . [NagasakiHA_10_28_2010_03_23
. . . . . . . . . . . . . . . . . . . . . with 22I,
. . . . . . . . . . . . . . . NagasakiHA_10_26_2010_03_15
. . . . . . . . . . . . . . . . . . . . . with 22I, syn103E,
. . . . . . . . . . . . . . . NagasakiHA_10_24_2010_03_08
. . . . . . . . . . . . . . . . . . . . . with syn103E,
. . . . . . . . . . . . . . . GuangxiLonganSWL1990_2010_02_08
. . . . . . . . . . . . . . . . . . . . . with 453K, syn462E,
. . . . . . . . . . . . . . . JiangxiDonghuSWL15_2010_01_04
. . . . . . . . . . . . . . . . . . . . . with syn106E, 149R, syn456L (TTg),
. . . . . . . . . . . . . . . ViennaINS142_2009_11_26
. . . . . . . . . . . . . . . . . . . . . with syn97D, 99T,
. . . . . . . . . . . . . . . CzechUsti208_2009_11_25
. . . . . . . . . . . . . . . . . . . . . with 268T,
. . . . . . . . . . . . . . . GhanaFS_1921_2009_11_11,
. . . . . . . . . . . . . . . Alaska44_2009_11_17
. . . . . . . . . . . . . . . . . . . . . with syn275V, 276N,
. . . . . . . . . . . . . . . CalifVRDL76_2009_09_21
. . . . . . . . . . . . . . . . . . . . . with syn283Q,
. . . . . . . . . . . . . . . Taiwan206_2009_09_18,
. . . . . . . . . . . . . . . Taiwan177_2009_09_18,
. . . . . . . . . . . . . . . Taiwan167_2009_09_18,
. . . . . . . . . . . . . . . Taiwan156_2009_09_18,
. . . . . . . . . . . . . . . Taiwan143_2009_09_15
. . . . . . . . . . . . . . . . . . . . . with 205E mix,
. . . . . . . . . . . . . . . Utah20_C2_2_2009_07_25_VxX
. . . . . . . . . . . . . . . . . . . . . with 159D, 206S, 227G
. . . . . . . . . . . . . . . Slovenia2687_2009_07_01
. . . . . . . . . . . . . . . . . . . . . with 35I, 206S],
. . . . . . . . syn456L [H5N1],
. . . . . . . . 463V,
. . . . . . . . 523A [Nebraska02_2010_03_11,
. . . . . . . . . . . . NagasakiHA1022_2010_03_01_syn413K,
. . . . . . . . . . . . DomRepublic3768_2009_12_15,
. . . . . . . . . . . . NY6939_2009_12_11,
. . . . . . . . . . . . CalifVRDL115_2009_12_04,
. . . . . . . . . . . . NY6607_2009_11_24,
. . . . . . . . . . . . RheinlandPfalz81_2009_11_23,
. . . . . . . . . . . . Berlin210_2009_11_16,
. . . . . . . . . . . . BadenWurttemberg511_2009_11_16,
. . . . . . . . . . . . CalifVRDL107_2009_11_15,
. . . . . . . . . . . . FL_Pensacola40_2009_11_09,
. . . . . . . . . . . . CalifVRDL101_2009_11_05,
. . . . . . . . . . . . DC114_2009_11_04,
. . . . . . . . . . . . Calif_SD35_2009_10_26,
. . . . . . . . . . . . NY5447_2009_10_23,
. . . . . . . . . . . . CalifVRDL84_2009_10_09,
. . . . . . . . . . . . CalifVRDL87_2009_10_09,
. . . . . . . . . . . . KuwaitN13013_2009_08_31_syn413K])

Supporting Sequences

. . . . CalifVRDL115_2009_12_04 (
. . . . . . . . . . . . 35I [H5N1],
. . . . . . . . . . . . 77N,
. . . . . . . . . . . . syn152I,
. . . . . . . . . . . . syn219I,
. . . . . . . . . . . . syn276H [1918, S5],
. . . . . . . . . . . . syn456L [H5N1],
. . . . . . . . . . . . 463V,
. . . . . . . . . . . . 523A)

. . . . FL_Pen213_2009_11_17 (
. . . . . . . . . . . . 35I [H5N1],
. . . . . . . . . . . . syn152I,
. . . . . . . . . . . . syn219I,
. . . . . . . . . . . . 273A,
. . . . . . . . . . . . syn276H [1918, S5],
. . . . . . . . . . . . syn456L [H5N1],
. . . . . . . . . . . . 463V,
. . . . . . . . . . . . 523A)

. . . . CalifVRDL107_2009_11_15 (
. . . . . . . . . . . . 35I [H5N1],
. . . . . . . . . . . . 39N,
. . . . . . . . . . . . syn152I,
. . . . . . . . . . . . syn219I,
. . . . . . . . . . . . syn276H [1918, S5],
. . . . . . . . . . . . syn456L [H5N1],
. . . . . . . . . . . . 463V,
. . . . . . . . . . . . 523A)

. . . . KoreaAF2376_2009_10_27 (
. . . . . . . . 88P [H2N3, H5N1, H11],
. . . . . . . . . . . . [Victoria508_2010_07_24 with ext changes,
. . . . . . . . . . . HunanHechengSWL1616_2009-11-23,
. . . . . . . . . . . Nevada15_9F_2009_09_10,
. . . . . . . . . . . GermanyCologne13_2009_06_29],
. . . . . . . . 131P,
. . . . . . . . 280A,
. . . . . . . . 290K [HunanHechengSWL1617_2009_11_23],
. . . . . . . . HA truncated after aa386)

. . . . Nevada15_9F_2009_09_10 (
. . . . . . . . 22I,
. . . . . . . . 88P,
. . . . . . . . 225E,
. . . . . . . . 256F,
. . . . . . . . 299Y,
. . . . . . . . 300S,
. . . . . . . . syn384S)

. . . . GermanyCologne13_2009_06_29 (
. . . . . . . . HA truncated until aa28,
. . . . . . . . 35I,
. . . . . . . . 38V,
. . . . . . . . 88P,
. . . . . . . . syn108L,
. . . . . . . . syn205G,
. . . . . . . . 206S,
. . . . . . . . syn276H,
. . . . . . . . HA truncated after aa321)




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