TamiFlu Resistant Washington State Sequence of April 2010 Accumulates 20 Worldwide HA Polymorphisms

Last Updated 2010-08-07

** This study is in an intermediate phase and will have additions and corrections. **

Avian and other zoonotic additions continue to accumulate in a disproportionate fashion onto human pandemic strains.  This sequence from a human case in the American coastal state of Washington demonstrates the hyper-morphic behaviour of this pandemic virus that has been frequently discussed in the studies on this website.  More than 15 months into the development of the pandemic reservoir, we see an acceleration of viral genetic acquisition / development, rather than the deceleration that has been promoted in the social messaging campaigns of many countries.

The PF11 viral reservoir (pH1N1) does not show signals of stability.

Anti-viral drug resistance is increasing on the trajectory predicted by our team. Multi-drug resistance is on the rise as well. As seen very recently in seasonal influenza, drug resistance may become fixed over the course of a single season given very low counts / percentages of seed strains starting the season with resistance.

Two recent sequence deposits from Japan (7 TmX in the most recent) included a high percentage of drug resistant sequences bringing the total number of deposited strains for Asia and North America alone to the threshold of 100. Those 100 strains that have been deposited most certainly under-represent confirmed case counts of drug resistance. But even those admitted 100 ancestral beds are plentiful donors to drive viral revision with the additional assistance of widespread, worldwide clinical / sub-clinical anti-viral drug usage due to treatment guideline modifications.

The Washington sequence profiled is remarkable from several viewpoints, including TamiFlu resistance, hyper-morphic behaviour at a record pace, the relatively high potential for multiple, sub-unit genetic acquisition and the gravity of the related / donor strains on vaccine escape and fatality. Several groups of changes on this sequence have not been found together in this pandemic reservoir database making this virus novel under more than one inspection criteria.


TamiFlu resistant strain in April 2010, US.

Washington01_2010_04_02_TmX

HA segment: 20 changes with 7 mixtures (5 with wt)
NA segment: 13 changes with 3 mixtures (2 with wt)

. . . . Washington01_2010_04_02_TmX (
. . . . . . . . #8A mix wt [NY7426_2009_12_08
. . . . . . . . . . . . . . . . . . . . with 0I, 441H, et al],
. . . . . . . . 10H mix wt,
. . . . . . . . 35I [H5N1],
. . . . . . . . 122N mix wt [H5N1 Egypt (ORF)],
. . . . . . . . . . . . . . . . [OrenburgIIV13E_2010_03_02_xL_f
. . . . . . . . . . . . . . . . . . . . with 165N, 225G, syn413K, et al,
. . . . . . . . . . . . . . . . Athens157_2009_12_21,
. . . . . . . . . . . . . . . . Athens257_2009_12_13,
. . . . . . . . . . . . . . . . Netherlands1493b_2009_10_23,
. . . . . . . . . . . . . . . . Oklahoma503_2009_08,
. . . . . . . . . . . . . . . . Niigata717_2009_06_23 mix wt
. . . . . . . . . . . . . . . . . . . . with 414I only,
. . . . . . . . . . . . . . . . Oklahoma2952_2009_04_28,
. . . . . . . . . . . . . . . . swNC19646_2010_04_20
. . . . . . . . . . . . . . . . . . . . with 158E, 186P, syn413K, et al],
. . . . . . . . 128D [H5N1],
. . . . . . . . . . . [GermanyBY74_2009
. . . . . . . . . . . . . . . . . with 128D, 225E and 226R,
. . . . . . . . . . . Oz_Victoria800_2010_06_02
. . . . . . . . . . . . . . . . . . . . . . with 502K,
. . . . . . . . . . . Kenya0042_2009_10_22 with 225E,
. . . . . . . . . . . Netherlands1064b_2009_09_01 with 225G GGa,
. . . . . . . . . . . SingSS003_2010_04 with 225G,
. . . . . . . . . . . SingSS004_2010_04 with 225G],
. . . . . . . . 131P [PF11 Conserved in Asia],
. . . . . . . . 131T [Perth29_2009_05_26,
. . . . . . . . . . . Catalonia362_2009_06_16],
. . . . . . . . 132T [Calif07_2010_04_23],
. . . . . . . . 145R [Montana02_2010_04_07_VxX
. . . . . . . . . . . . . . . with 42E, 159I, 377K, et al,
. . . . . . . . . . Montana03_2010_04_07
. . . . . . . . . . . . . . . with 42E, 159I, 377K, et al,
. . . . . . . . . . Montana01M1C1_2010_04_04
. . . . . . . . . . . . . . . with 42E, 159I, 377K, et al,
. . . . . . . . . . Kansas04_2010_04_01
. . . . . . . . . . . . . . . with 42E, 377K, et al,
. . . . . . . . . . Wyoming02_2010_04_21
. . . . . . . . . . . . . . . with 42E, 377K, et al,
. . . . . . . . . . Calif07_2010_04_23
. . . . . . . . . . . . . . . with 42E, 132T, 377K, et al,
. . . . . . . . . . Nevada02_2010_05_24
. . . . . . . . . . . . . . . with 42E, 377K, et al,
. . . . . . . . . . Connecticut02_2010_04_05
. . . . . . . . . . . . . . . with 42E, 377K, et al,
. . . . . . . . . . Connecticut03_2010_05_06
. . . . . . . . . . . . . . . with 42E, 377K, et al,
. . . . . . . . . . NagasakiHA_10_1_2010_01_04
. . . . . . . . . . . . . . . with syn413K,
. . . . . . . . . . Athens268_2009_12_15,
. . . . . . . . . . Rome636_2009_11_26,
. . . . . . . . . . Calif_SD68_2009_11_03,
. . . . . . . . . . Kenya0046_2009_10_23],
. . . . . . . . syn159N [H3N8, H9N2],
. . . . . . . . . . . [IndiaDelhi3704_2009_09,
. . . . . . . . . . . Orenburg2974_2009_11_16_xL with 225N,
. . . . . . . . . . . YaroslavlIIV196_2009_12_04_f with 225G,
. . . . . . . . . . . NY7420_2010_01_02,
. . . . . . . . . . . NY7425_2009_12_20,
. . . . . . . . . . . California, Texas, Wisconsin,
. . . . . . . . . . . Nebraska01_2010_01_28 with syn485G,
. . . . . . . . . . . Scandinavia, Italy,
. . . . . . . . . . . Brussels243_2009_11_09 with 89G,
. . . . . . . . . . . Australia35_2009_07_24
. . . . . . . . . . . . . . with 89G and 504E,
. . . . . . . . . . . Australia6_2009_07_18
. . . . . . . . . . . . . . with 89G and 233H],
. . . . . . . . 186P,
. . . . . . . . 188N,
. . . . . . . . 219G [Unique to PF11],
. . . . . . . . 219R [Unique to PF11],
. . . . . . . . 241G,
. . . . . . . . 265E,
. . . . . . . . syn361G mix wt [1918, WSN33, tn],
. . . . . . . . . . . . . . . . . . [NY6943_2009_12_07_xL],
. . . . . . . . 377K mix wt [H9N2],
. . . . . . . . syn413K [H9N2],
. . . . . . . . syn441H [H2, H5N1, H6, H9N2, H11],
. . . . . . . . . . . . . . . [Moscow_BVA_2009_10_24_xL_f with 225G,
. . . . . . . . . . . . . . Russia12_2009_11_01_xL,
. . . . . . . . . . . . . . NY1998_2010_01_18 with 100N,
. . . . . . . . . . . . . . NY7420_2010_01_02,
. . . . . . . . . . . . . . NY7425_2009_12_20,
. . . . . . . . . . . . . . NY7426_2009_12_08 with 0I,
. . . . . . . . . . . . . . Calif_SD75_2009_11_12,
. . . . . . . . . . . . . . CalifVRDL34_2009_06_30,
. . . . . . . . . . . . . . TexasJMS362_2009_11_07,
. . . . . . . . . . . . . . Washington72_2009_11_25 with 193N,
. . . . . . . . . . . . . . WiscD2442_2009_10_12,
. . . . . . . . . . . . . . ferretOregon23775_2009_10_05])

NA

. . . . Washington01_2010_04_02_TmX (
. . . . . . . . 248N,
. . . . . . . . 275Y,
. . . . . . . . 276F,
. . . . . . . . 365N,
. . . . . . . . syn369N,
. . . . . . . . 382E mix wt,
. . . . . . . . 394I,
. . . . . . . . 395E mix wt,
. . . . . . . . syn412L,
. . . . . . . . 434D (gAa)
. . . . . . . . 434K (aAa),
. . . . . . . . syn458P,
. . . . . . . . 463V)


Supporting Sequences
HA

. . . . Orenburg2974_2009_11_16_xL (
. . . . . . . . 34D [NewYork, Arizona, California],
. . . . . . . . syn159N [H3N8, H9N2]
. . . . . . . . . . . . . . [IndiaDelhi3704_2009_09,
. . . . . . . . . . . . . . NY, California, Texas, Wisconsin,
. . . . . . . . . . . . . . Scandinavia, Italy, et al],
. . . . . . . . 225N,
. . . . . . . . 313I [Unique to PF11],
. . . . . . . . syn372Q [H2, H3N8, H4, H5, H6, H7N3, H7N7, H9N2, H11]
. . . . . . . . . . . . . . [IndiaPune9355_2009_08 with 225G,
. . . . . . . . . . . . . . IndiaBlore236_2009_06 with 226R,
. . . . . . . . . . . . . . Ulyanovsk_SHTA_2009_10_31_f_225N,
. . . . . . . . . . . . . . Russia fatal extensive,
. . . . . . . . . . . . . . swIowa35572_2009_12_16,
. . . . . . . . . . . . . . NagasakiHA10_22_2010_03_01],
. . . . . . . . syn413K [H9N2],
. . . . . . . . syn485G [Nebraska 01_2010_01_28,
. . . . . . . . . . . . . . IndiaPune10604_2009_09,
. . . . . . . . . . . . . . NagasakiHA10_22_2010_03_01],
. . . . . . . . syn513I [Kansas26_2009_11_03,
. . . . . . . . . . . . . . Texas46201823_2009_10_20]),

. . . . YaroslavlIIV196_2009_12_04_f (
. . . . . . . . . . . syn7C,
. . . . . . . . . . . 89G [H7N7],
. . . . . . . . . . . syn159N [H3N8, H9N2],
. . . . . . . . . . . 225G,
. . . . . . . . . . . syn297N [H5N1],
. . . . . . . . . . . syn319T [H5N1],
. . . . . . . . . . . syn428L [H5N1]),

. . . . OrenburgIIV13E_2010_03_02_xL_f (
. . . . . . . . #11T,
. . . . . . . . 122N
. . . . . . . . 165N [H9N2],
. . . . . . . . syn168Y [H9N2],
. . . . . . . . 225G,
. . . . . . . . 238K,
. . . . . . . . syn413K [H2, H5N1, H9N2]),

. . . . OrenburgIIV13_2010_03_02_xL_f (
. . . . . . . . #11T,
. . . . . . . . 165N [H9N2],
. . . . . . . . syn168Y [H9N2],
. . . . . . . . 225G,
. . . . . . . . 238K,
. . . . . . . . syn413K [H2, H5N1, H9N2]),

. . . . Niigata717_2009_06_23 (
. . . . . . . . 122N mix wt [H5N1 Egypt (ORF)],
. . . . . . . . . . . . . . . . [OrenburgIIV13E_2010_03_02_xL_f
. . . . . . . . . . . . . . . . . . . . with 165N, 225G, syn413K, et al,
. . . . . . . . . . . . . . . . Washington01_2010_04_02_TmX
. . . . . . . . . . . . . . . . . . . with 20 HA polymorphisms,
. . . . . . . . . . . . . . . . Athens157_2009_12_21,
. . . . . . . . . . . . . . . . Athens257_2009_12_13,
. . . . . . . . . . . . . . . . Netherlands1493b_2009_10_23,
. . . . . . . . . . . . . . . . Oklahoma503_2009_08,
. . . . . . . . . . . . . . . . Niigata717_2009_06_23 mix wt
. . . . . . . . . . . . . . . . . . . . with 414I only,
. . . . . . . . . . . . . . . . Oklahoma2952_2009_04_28,
. . . . . . . . . . . . . . . . swNC19646_2010_04_20
. . . . . . . . . . . . . . . . . . . . with 158E, 186P, syn413K, et al],
. . . . . . . . 206T,
. . . . . . . . 414I),

. . . . NY7426_2009_12_08 (
. . . . . . . . #8A, 0I, 35I, syn69E, syn154L, syn159N,
. . . . . . . . 175K, 206T, syn413K, syn441H,
. . . . . . . . syn538F [GuamNHRC0002_2009_07_23]),

. . . . SingSS003_2010_04 (
. . . . . . . . syn44L,
. . . . . . . . syn94Y,
. . . . . . . . syn106E,
. . . . . . . . 128D [H5N1],
. . . . . . . . . . . [GermanyBY74_2009
. . . . . . . . . . . . . . . . . with 128D, 225E and 226R,
. . . . . . . . . . . Kenya0042_2009_10_22 with 225E,
. . . . . . . . . . . Netherlands1064b_2009_09_01 with 225G GGa,
. . . . . . . . . . . Oz_Victoria800_2010_06_02 with 502K,
. . . . . . . . . . . SingSS004_2010_04 with 225G],
. . . . . . . . 225G,
. . . . . . . . syn295F,
. . . . . . . . 377K [H9N2]),
. . . . SingSS004_2010_04 (
. . . . . . . . syn44L,
. . . . . . . . 51T,
. . . . . . . . syn106E,
. . . . . . . . 128D [H5N1],
. . . . . . . . . . . [GermanyBY74_2009
. . . . . . . . . . . . . . . . . with 128D, 225E and 226R,
. . . . . . . . . . . Kenya0042_2009_10_22 with 225E,
. . . . . . . . . . . Netherlands1064b_2009_09_01 with 225G GGa,
. . . . . . . . . . . Oz_Victoria800_2010_06_02 with 502K,
. . . . . . . . . . . SingSS003_2010_04 with 225G],
. . . . . . . . 225G,
. . . . . . . . 377K [H9N2]),

. . . . GuamNHRC0002_2009_07_23 (
. . . . . . . . syn231N,
. . . . . . . . syn538F [NY7426_2009_12_08]),

. . . . Oz_Victoria800_2010_06_02 (
. . . . . . . . syn44L,
. . . . . . . . syn106E,
. . . . . . . . 128D [H5N1],
. . . . . . . . . . . [GermanyBY74_2009
. . . . . . . . . . . . . . . . . with 128D, 225E and 226R,
. . . . . . . . . . . Kenya0042_2009_10_22 with 225E,
. . . . . . . . . . . Netherlands1064b_2009_09_01 with 225G GGa,
. . . . . . . . . . . SingSS003_2010_04 with 225G,
. . . . . . . . . . . SingSS004_2010_04 with 225G],
. . . . . . . . 206T,
. . . . . . . . 377K [H9N2],
. . . . . . . . 502K [UkrTernopilN10_2009_10_28_xL_f with 225G,
. . . . . . . . . . . SingGP2362_2010_05_18,
. . . . . . . . . . . Scandinavia (7),
. . . . . . . . . . . CalifVRDL2_2010_01_11,
. . . . . . . . . . . California33_2009_08_06,
. . . . . . . . . . . Michigan21_2009_08_07,
. . . . . . . . . . . SouthCarolina36_2009_09_02,
. . . . . . . . . . . SouthCarolina38_2009_09_17,
. . . . . . . . . . . Haiti534_2009_10_19,
. . . . . . . . . . . AlgeriaG2902_2009_12_09 mix with 225E,
. . . . . . . . . . . Egypt114_2009_12_06 with 225E,
. . . . . . . . . . . JapanPR1070_2009_07_10,
. . . . . . . . . . . ThailandTHB0438_2009_07_28,
. . . . . . . . . . . Jiangyin34_2009_08_16,
. . . . . . . . . . . GuangxiLongan1870_2009_12_16],
. . . . . . . . syn529L)

Additional supporting sequences may be viewed on the recently updated study indicating that 100% of the critical HA range between aa186 and aa248 has registered changes within the PF11 reservoir.  Consistent spread is apparent with a March to June expansion of one Hydra strain from the US to the Ukraine and back.

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