TamiFlu Resistance and HA Diversity in Japan

7 Anti-Viral resistant sequences from Japan on 5 Different HA Backgrounds between October 27, 2009 and January 2010. 

The Kumamoto sequence carries 8 HA polymorphisms, joining the recent cast of hyper-morphic, Russian fatalities.  Of the HA revisions on the TamiFlu-resistant Kumamoto case, 5 are found on various animal (zoonotic) influenza sequences like H3N8, H5N1, H7N7 and H9N2 (domestic poultry). 

An examination of the RnR polymorphisms (Rare, not Random), shows at least one change appears on a fatality case from Italy and at least one silent polymorphism that is found in an alternate coding on an Avian-influenced, cross-linked sequence.  Trackback via the dates and locations of each change to find the ultimate origin (as far as the GenBank database is concerned) for each polymorphism.  Note that several potential donor sequences carry more than one of the markers on the Kumamoto case.

. . . . Kumamoto2_2010_01_14_TmX (
. . . . . . . . syn10Y [China22811_2009_12
. . . . . . . . . . . . . . . . . . . with 14 HA changes],
. . . . . . . . 252L [Maryland03_2010_01_13,
. . . . . . . . . . . . Guangdong2361_2009_11_25],
. . . . . . . . syn254P [1918, tn, H5N1]),
. . . . . . . . . . . . . . [Ancona451_2009_11_27_f,
. . . . . . . . . . . . . .  Iran15583_2009_11_21
. . . . . . . . . . . . . . . . . . with 16 HA (226R) + 3 NA changes,
. . . . . . . . . . . . . . Iran16677_2009_11_24],
. . . . . . . . syn320G [H5N1],
. . . . . . . . . . . . . . [Yamagata307_2009_09_24
. . . . . . . . . . . . . . . . . . . with 123T, syn134G,
. . . . . . . . . . . . . . Moscow_ION_2009_07_16,
. . . . . . . . . . . . . . Bolivia1263_2009_07_14 with syn107Q,
. . . . . . . . . . . . . . Mie41_2009_07_11 with syn107Q]
. . . . . . . . syn366A (GCa) [H5N1],
. . . . . . . . . . . . . . [Unique to PF11 Asia,
. . . . . . . . . . . . . . Netherlands2143_2009_11_16,
. . . . . . . . . . . . . . Maryland31_2009_11_09,
. . . . . . . . . . . . . . Calif_SD35_2009_10_26,
. . . . . . . . . . . . . . NY5297_2009_10_22,
. . . . . . . . . . . . . . NorthCarolina53_2009_10_18,
. . . . . . . . . . . . . . Stockholm67_2009_07_17,
. . . . . . . . . . . . . . MauritusMPn_2009_07_01,
. . . . . . . . . . . . . . MauritusMPt_2009_07_01,
. . . . . . . . . . . . . . ENG92860032_2009_07,
. . . . . . . . . . . . . . ENG520_2009_06,
. . . . . . . . . . . . . . ENG507_2009_06,
. . . . . . . . . . . . . . WiscS1416_2009_10_26_xL (GCt),
. . . . . . . . . . . . . . TexasJMS385_2009_12_04 (GCt)],
. . . . . . . . syn390N [H2, H3N8, H5, H6, H7N3, H7N7, H9N2, H11],
. . . . . . . . . . . . . . [Calif09_2010_05_11,
. . . . . . . . . . . . . .  NY7480_2010_03_01,
. . . . . . . . . . . . . .  NY03_2010_02_09,
. . . . . . . . . . . . . .  Texas01_2010_01_13,
. . . . . . . . . . . . . .  TexasJMS400_2009_12_31,
. . . . . . . . . . . . . .  TexasJMS399_2009_12_31,
. . . . . . . . . . . . . .  TexasJMS398_2009_12_30,
. . . . . . . . . . . . . .  TexasJMS397_2009_12_30,
. . . . . . . . . . . . . .  Washington73_2009_12_14,
. . . . . . . . . . . . . .  NY6937_2009_12_11,
. . . . . . . . . . . . . .  Bishkek03_2009_11_28
. . . . . . . . . . . . . .. . . . . . . . . . with syn131S, 175D,
. . . . . . . . . . . . . .  Tomsk06_2009_11_22,
. . . . . . . . . . . . . .  Russia200_2009_11_01
. . . . . . . . . . . . . .. . . . . . . . . . with syn131S, 175D,
. . . . . . . . . . . . . .  NY5196_2009_10_20,
. . . . . . . . . . . . . .  NY5141_2009_10_16
. . . . . . . . . . . . . .. . . . . . . . . . with syn131S,
. . . . . . . . . . . . . .  ENG94280034_2009_10_06,
. . . . . . . . . . . . . .  Texas45093846_2009,
. . . . . . . . . . . . . .  Texas45024243_2009,
. . . . . . . . . . . . . .  AfghanistanN10786_2009_09_07
. . . . . . . . . . . . . .. . . . . . . . . . with syn131S,
. . . . . . . . . . . . . .  AfghanistanN10760_2009_09
. . . . . . . . . . . . . .. . . . . . . . . . with syn131S,
. . . . . . . . . . . . . .  AfghanistanN09787_2009_08
. . . . . . . . . . . . . .. . . . . . . . . . with syn131S,
. . . . . . . . . . . . . .  Nepal (Nov)
. . . . . . . . . . . . . .  NeimengguHuimin11560_2009_12_30,
. . . . . . . . . . . . . .  Kentucky16_2009_07_30],
. . . . . . . . syn466G [H5N1, tn],
. . . . . . . . . . . . . . [Unique to PF11 Japan,
. . . . . . . . . . . . . . ChongqingYuzhong11307_2009_12_15
. . . . . . . . . . . . . .. . . . . . . . . . with 219V,
. . . . . . . . . . . . . . NY6864_2009_12_02
. . . . . . . . . . . . . .. . . . . . . . . . with 530I,
. . . . . . . . . . . . . . NY6909_2009_11_29
. . . . . . . . . . . . . .. . . . . . . . . . with 530I,
. . . . . . . . . . . . . . GuangdongHaizhu1644_2009_11_25,
. . . . . . . . . . . . . . NY6675_2009_11_24
. . . . . . . . . . . . . .. . . . . . . . . . with 530I,
. . . . . . . . . . . . . . DC46_2009_11_03
. . . . . . . . . . . . . .. . . . . . . . . . with 530I,
. . . . . . . . . . . . . . NY4995_2009_10_04
. . . . . . . . . . . . . .. . . . . . . . . . with 530I,
. . . . . . . . . . . . . . CalifVRDL75_2009_09_19
. . . . . . . . . . . . . .. . . . . . . . . . with 119M,
. . . . . . . . . . . . . . Texas45130742_2009_09_13,
. . . . . . . . . . . . . .. . . . . . . . . . with syn227E,
. . . . . . . . . . . . . . Texas45132788_2009_09_13,
. . . . . . . . . . . . . . Texas45120922_2009_09_12,
. . . . . . . . . . . . . . Texas45122282_2009_09_12,
. . . . . . . . . . . . . . Texas45113882_2009_09_11],
. . . . . . . . syn548C [H5N1, 1918, tn]
. . . . . . . . . . . . . . [Unique to PF11 Asia,
. . . . . . . . . . . . . . Bishkek03_2009_11_28
. . . . . . . . . . . . . .. . . . . . . . . . with syn131S, 175D,
. . . . . . . . . . . . . . Russia200_2009_11_01
. . . . . . . . . . . . . .. . . . . . . . . . with syn131S, 175D,
. . . . . . . . . . . . . . NY5141_2009_10_16
. . . . . . . . . . . . . .. . . . . . . . . . with syn131S,
. . . . . . . . . . . . . . AfghanistanN10786_2009_09_07
. . . . . . . . . . . . . .. . . . . . . . . . with syn131S,
. . . . . . . . . . . . . . AfghanistanN10760_2009_09
. . . . . . . . . . . . . .. . . . . . . . . . with syn131S,
. . . . . . . . . . . . . . AfghanistanN09787_2009_08
. . . . . . . . . . . . . .. . . . . . . . . . with syn131S])

. . . . Okayama1_2010_01_04_TmX (
. . . . . . . . #2I,
. . . . . . . . syn134G,
. . . . . . . . syn143G,
. . . . . . . . 241N mix wt,
. . . . . . . . 327V,
. . . . . . . . syn413K,
. . . . . . . . syn482V),
. . . . Aichi1222_2009_11_27_TmX (
. . . . . . . . syn134G,
. . . . . . . . syn236L,
. . . . . . . . 298L,
. . . . . . . . syn413K,
. . . . . . . . syn492Y),
. . . . Miyagi170_2009_10_27_TmX (
. . . . . . . . syn134G,
. . . . . . . . syn413K,
. . . . . . . . syn482V),

. . . . Niigata_C186_2009_12_25_TmX (
. . . . . . . . 87N,
. . . . . . . . 135E,
. . . . . . . . 377K),
. . . . Shizuoka_C442_2009_12_19_TmX (
. . . . . . . . 71G,
. . . . . . . . 377G,
. . . . . . . . syn413K),
. . . . Shizuoka_C21_2010_01_20_TmX (
. . . . . . . . 22I,
. . . . . . . . syn149K,
. . . . . . . . syn413K,
. . . . . . . . 523A [Extensive US 2010 April & May (10),
. . . . . . . . . . . .  on entirely different background,
. . . . . . . . . . . .  including Montana02_2010_04_07_VxX]),

Supporting Sequences
HA

. . . . Moscow_ION_2009_07_16 (
. . . . . . . . syn70C [H2N3, H3N8, H5, H6, H7N7],
. . . . . . . . syn158G [H3N8],
. . . . . . . . . . . . . . . [NY4748_2009_07 with 163E,
. . . . . . . . . . . . . . . Mongolia_Inner01_2009_07_27 with 89G,
. . . . . . . . . . . . . . . swNC13598_2010_03_09_f_xL
. . . . . . . . . . . . . . . . . . . . . . . . with 15 HA + 4 NA revisions],
. . . . . . . . 206T,
. . . . . . . . syn320G [H5N1],
. . . . . . . . . . . [Kumamoto2_2010_01_14_TmX,
. . . . . . . . . . . Yamagata307_2009_09_24,
. . . . . . . . . . . Bolivia1263_2009_07_14,
. . . . . . . . . . . Mie41_2009_07_11],
. . . . . . . . syn542S [H2, H5N1, H9N2])

In the United States the state of Washington has demonstrated a hyper-morphic, TamiFlu resistant strain during April 2010.

Please refer to additional studies for further genetic analyses, including the survey on amino acid revisions potentially related to Vaccine Escape.

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