HA 230I with 225N Demonstrated in Iowa Swine during November 2009

Last Updated 2010-11-08

On 2010-11-01, a collaboration of researchers based in Ames, Iowa deposited a swine sequence at GenBank.  November 2009 is the sample month, approximately one year prior to publication.  The first instance of the dual RBD change 225N and 230I is found in this swine data.

Though the HA is hyper-morphic, the cross-linked Iowa swine has only one NA change (syn414G) other than the cross-linkage syn407V for a total of 2 silent changes.  Those two changes on the NA appear only in a single pandemic sequence, Liaoning_HepingSWL1606_13M_2009_12_23.  The two changes (syn407V with syn414G) also appear in 16 recent H5N1 (2006-2009) sequences: 2 human, 10 birds and 4 environmental.

The potential HA recombinant appears to be on a pandemic H1N1 background with multiple donation bases from S7 H1N1 and S7 & S5 H1N2 including several blocks coding for contiguous amino acid revision.  The swine HA sequence has 92% homology to the nearest HA.  More than 100 changes are demonstrated on the swine HA, the bulk of which appear on Seasonal H1N1 2007.

swIowa44837_1_2009_11_08_xL carries a universe of changes suggestive as a progenitor of / donor to the recently discussed emergence of a 230I-permissive sub-clade.  The swine matches and domaining are evident around several of the six markers for the new sub-clade as well as around several non-marker polymorphisms from the emerging sub-clade sequences.

Furthermore, this single swine sequence also carries markers implicated in the cross-linked Russian fatality analysis.  An annotated chart was developed to investigate the various paths to fatality in Russia, determining that high genetic lability existed for fatal outcomes and that changes at amino acid 225 were not required to produce fatal outcomes.  The group of fatal sequences from Moscow and Ivanovo in the bottom right of the annotated phylogenetic tree carries a large number of changes including the syn355H found on the swine sequence under review in this analysis.  The opposed group of fatal sequences from Ulyanovsk in the top left of the chart carries the smallest count of changes from the larger deposit and includes the syn372Q found on swIowa44837_1_2009_11_08_xL.

Similar sequences to this Iowa swine recombinant have been recorded circulating throughout the United States in Minnesota, North Carolina, Illinois and Indiana during late 2009 and early 2010 including:

swMinnesota02979_2010_02_17
swMinnesota02976_2010_01_12
swIllinois3910_2010_01_11
swIllinois02957_2010
swIllinois02960_2010
swIllinois02938_2009-12-29
swIllinois02935_2009_12_20
swIllinois02936_2009_12_20
swIllinois02919_2009_11_12
swIllinois32975_2009_11_11
swNorthCarolina02926_2009_11_24
swIndiana27007_2009

. . . . swIowa44837_1_2009_11_08_xL (
. . . . . . . . Hyper-morphic HA recombinant on PF11 background
. . . . . . . . with multiple donation bases from S7 H1N1 and S7 & S5 H1N2:
. . . . . . . . ~ 92% Homology to nearest HA
. . . . . . . . with more than 100 changes including, but not limited to:
. . . . . . . . syn36L,
. . . . . . . . syn38E,
. . . . . . . . syn40H,
. . . . . . . . syn41N,
. . . . . . . . syn42G,
. . . . . . . . 48K [S7],
. . . . . . . . syn49G,
. . . . . . . . 50I [S7],
. . . . . . . . syn56G, syn58C, syn70C, syn86S, 92M,
. . . . . . . . 131S,
. . . . . . . . 132T [S7],
. . . . . . . . 156E [swCloppenIDT4777_S5_H1N2,
. . . . . . . . . . . . . swDoetIDT4735_S5_H1N2],
. . . . . . . . syn169I, syn170N, 171E,
. . . . . . . . 182V [S7],
. . . . . . . . . . . . . [NY7480_2010_03_01 with 253A],
. . . . . . . . 188R,
. . . . . . . . 189G [S7],
. . . . . . . . 193G,
. . . . . . . . 196H [S7],
. . . . . . . . 197H,
. . . . . . . . 198E [S7],
. . . . . . . . 199N [S7],
. . . . . . . . 214T [S7],
. . . . . . . . syn222K [S7],
. . . . . . . . syn224R [S7],
. . . . . . . . 225N [swCloppenIDT4777_S5_H1N2,
. . . . . . . . . . . . . swDoetIDT4735_S5_H1N2],
. . . . . . . . syn226Q [S7],
. . . . . . . . syn228G [S7],
. . . . . . . . 230I [S7],
. . . . . . . . syn232Y [S7],
. . . . . . . . syn235T [S7],
. . . . . . . . 238D [H2N3, H7N3, H7N7, tn, swine],
. . . . . . . . . . . . . [RussiaBelgorod2_2010_03_15
. . . . . . . . . . . . . . . . . . with 158E, 225G, 230I],
. . . . . . . . 241Y,
. . . . . . . . 244I [S7],
. . . . . . . . syn246E [S7],
. . . . . . . . . . . . . . . [TexasAF2579_2009_10_04 with 230I],
. . . . . . . . 248N,
. . . . . . . . syn251L,
. . . . . . . . 253A [NY7480_2010_03_01 with 182V],
. . . . . . . . 260L [S7],
. . . . . . . . 263G,
. . . . . . . . 264F [S7],
. . . . . . . . 272N [S7],
. . . . . . . . 273A [S7],
. . . . . . . . 275M [S7],
. . . . . . . . 276G,
. . . . . . . . 277E [S7],
. . . . . . . . 280A [MI09_2007_H1N2],
. . . . . . . . 281N,
. . . . . . . . 298V [S7],
. . . . . . . . 305E [swCloppenIDT4777_S5_H1N2,
. . . . . . . . . . . . . swDoetIDT4735_S5_H1N2],
. . . . . . . . syn329S [S7],
. . . . . . . . syn346G [S7],
. . . . . . . . . . . . . . . [H3N2, H3N8, H5N1, H6N2, H6N4, H10N7],
. . . . . . . . . . . . . . [Fixed in non-PF11 Emergent swine lineages,
. . . . . . . . . . . . . . swNC19646_2010_04_20 with 158E,
. . . . . . . . . . . . . . Minnesota04_2010_03_22 with 230I,
. . . . . . . . . . . . . . Nevada01_2010_01_02,
. . . . . . . . . . . . . . Nevada20_2009_12_03,
. . . . . . . . . . . . . . Sachsen180_2009_12_02,
. . . . . . . . . . . . . . Lisboa108_2009_11_30 with 225E, syn228G,
. . . . . . . . . . . . . . GhanaFS2206_2009_11_25 with syn228G,
. . . . . . . . . . . . . . GhanaFS1982_2009_11_16 with syn228G,
. . . . . . . . . . . . . . NewMexico16MXC1_2009_11_07,
. . . . . . . . . . . . . . BZ_RioJaneiro7131_2009_08_01_f],
. . . . . . . . syn355H [MI09_2007_H1N2,
. . . . . . . . . . . . . . . . swCloppenIDT4777_S5_H1N2,
. . . . . . . . . . . . . . . . swDoetIDT4735_S5_H1N2],
. . . . . . . . syn361G [S7],
. . . . . . . . syn372Q [S7],
. . . . . . . . 376N [MI09_2007_H1N2,
. . . . . . . . . . . . swCloppenIDT4777_S5_H1N2,
. . . . . . . . . . . . swDoetIDT4735_S5_H1N2],
. . . . . . . . syn379T [S7],
. . . . . . . . . . . . . . . [Wisconsin06_2010_04_28],
. . . . . . . . syn381K [S7],
. . . . . . . . syn382V [S7],
. . . . . . . . syn385V [S7],
. . . . . . . . syn388K [S7],
. . . . . . . . syn390N [S7],
. . . . . . . . . . . . . . . [H2, H3N8, H5, H6, H7N3, H7N7, H9N2, H11],
. . . . . . . . . . . . . . . [Calif09_2010_05_11],
. . . . . . . . syn391T [S7],
. . . . . . . . syn392Q [S7],
. . . . . . . . syn395A [S7],
. . . . . . . . syn396V [S7],
. . . . . . . . syn397G [S7],
. . . . . . . . syn399E [S7],
. . . . . . . . . . . . . . . [Arizona06_2010_05_29 with 158E],
. . . . . . . . syn403L [S7],
. . . . . . . . 405R [S7],
. . . . . . . . 407M [S7],
. . . . . . . . syn413K [S7],
. . . . . . . . syn419L [S7],
. . . . . . . . syn428L [S7],
. . . . . . . . syn443S [S7],
. . . . . . . . syn495E [MI09_2007_H1N2],
. . . . . . . . 508R,
. . . . . . . . syn515Q)

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