H5N1 Avian Markers, Side by Side, in 2011 Human pH1N1 Stockholm, Sweden Case

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 spreadsheet for completeness in citation.

Last Update
2011-09-20

On 2011-07-29, the UK National Institute for Medical Research published 29 pH1N1 sequences at GISAID.  These sequences were sampled from patients in Scandinavia, Eastern Europe, the Balkans and Hong Kong from January to May 2011 covering the second half of the Northern Hemisphere 2010-2011 season.  The Swedish Institute for Infectious Disease Control originated 10 of the samples in this Mill Hill deposit including a highly zoonotic and potential H5N1 recombinant, Stockholm13_2011_03_28, with no specified gender, age or outcome.

Two contiguous H5N1 Avian markers, HA 415E and 416N, each novel to the human H1N1 pandemic, appear in this human case.  The HA 416N is reported as a mixed peak trace, an output that is commonly interpreted as suggestive of multiple infecting strains.  The single H5N1 potential donor HA segment on file is also unusual in that this Egyptian domestic poultry sequence carries numerous homologies to polymorphisms found on human pH1N1 Clade 1 (189T) and Clade 2 (188T) sequences.  Several of those H5N1 to pH1N1 homologies are quite rare to H5N1, but are strongly emergent in pH1N1.

Stockholm13_2011_03_28 was sampled near the end of the traditional Northern Hemisphere influenza season and, as such, represents one probable foundation for ongoing Clade 2 transmission into the upcoming influenza season (2011-2012).  As has been regularly discussed, Clade 2 (188T) is the most prevalent numerically of the 5 major pH1N1 divisions as reported in the public and private genetic databases.  Being roughly par for the course, this Swedish sequence is hypermorphic, carrying 14 polymorphisms (9 Amino and 5 Silent).

Particular to the matter at hand, Clade 2 sequences have demonstrated a measurable propensity for accepting polymorphisms into pH1N1 and projecting those changes across pH1N1 (“Clade Jumping” / Clade Transfer).  The method and means continue under investigation, whether due to the influence of Avian H1N1 common ancestry from the primary donors into the major human pH1N1 clades or due to some form of recombination / attractant magnetism occurring between and among the human pH1N1 clades.

GeneWurx has tracked development of the H1N1 pandemic from the publicly accepted Contact Zero in early 2009 (and potential prequels) up to the present emergent strains.  As with prior H5N1 investigations, random variation remains far from the field of explanatory options in most cases.  Malleability by random mallet has not been shown as an important means of genetic variation in this H1N1 human pandemic.

The back-to-back polymorphisms transferring HA 415E and 416N onto the human pH1N1 Stockholm13_2011_03_28 sequence are noted in the H5N1 database.  That single H5N1 sequence is a human-adapted, avian case from Egypt.  This dual signal transfer demonstrates one very concrete case of cross-species, cross-serotype genetic transfer from an animal to a human serotype. 

H5N1 contiguous homology to the dominant clade in the dominant circulating human serotype (pH1N1) instructs the medical fraternity to the weight of emergent zoonoses and suggests that at least one avian flightpath may be worthy of investigation.

. . . . SwedenStockholm13_2011_03_28 (
. . . . . . . . PHz = 87%
. . . . . . . . PHzAv = 87%
. . . . . . . . GISAID HA EPI326240
. . . . . . . . 14 Polymorphisms (9 Amino and 5 Silent)
. . . . . . . . syn41N (AAt) [H5N1 Human Emergent with TamiFlu Resistance],
. . . . . . . . . . . . . . . . .  [H5N1 Egypt Human 2007],
. . . . . . . . . . . . . . . . .  [H5N1 Avian with 166I],
. . . . . . . . 50I [WSN_1933, WSZ_1933],
. . . . . . . . . .  [1918],
. . . . . . . . syn154L (tTA) [H3N2 Avian with 158E],
. . . . . . . . . . . . . . . . . . [H3N2 Canine, Feline wt]
. . . . . . . . . . . . . . . . . . [H3N2 Human wt (tTg)],
. . . . . . . . . . . . . . . . . . [H3N8 Avian (tTg)],
. . . . . . . . . . . . . . . . . . [H9N2 Avian with 404G],
. . . . . . . . . . . . . . . . . . [H9N2 Avian (tTg)],
. . . . . . . . . . . . . . . . . . [H9N2 Human with syn40H (tTg)],
. . . . . . . . 158E mix wt [H3N8, H5N1],
. . . . . . . . . . . . . . . . . [H3N2 Avian],
. . . . . . . . . . . . . . . . . . . . with 165N, 190E, 225G, 230I, 238K
. . . . . . . . . . . . . . . . . . . . . . . 253A, 275I, syn346G],
. . . . . . . . . . . . . . . . . [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . with #1T, 8V, syn31H, syn40H, syn42G,
. . . . . . . . . . . . . . . . . . . . . . . 72L, syn80S, syn82I, 87N, syn118E,
. . . . . . . . . . . . . . . . . . . . . . . 144E, 189T, 193R, 237I,
. . . . . . . . . . . . . . . . . . . . . . . syn287G, syn346G, 523A],
. . . . . . . . . . . . . . . . . [sw1930],
. . . . . . . . 188T [H6N1, H7N7],
. . . . . . . . . . . . [H10N7 Avian 2008
. . . . . . . . . . . . . . . . with #1V, 87N, syn94Y, 100N, syn102E,
. . . . . . . . . . . . . . . . . . . 156E, 157E, 163T, 165N,
. . . . . . . . . . . . . . . . . . . syn177L, 188T, syn221P, syn207S, syn213F,
. . . . . . . . . . . . . . . . . . . 225G, 230I, 233H, 237I, syn239P,
. . . . . . . . . . . . . . . . . . . syn338G, syn346G, syn356H,
. . . . . . . . . . . . . . . . . . . syn390N, syn391T],
. . . . . . . . . . . . [H1N1 Avian
. . . . . . . . . . . . . . . . with 186P, 189T,
. . . . . . . . . . . . . . . . . . . and extensive pH1N1_υ polymorphisms],
. . . . . . . . 259T [H9N2 Avian and Human (att)
. . . . . . . . . . . . . . . . with syn40H],
. . . . . . . . syn338G (GGc) [H3N2 Avian, Canine, Feline],
. . . . . . . . . . . . . . . . . . [H3N8, H4, H5N1 Avian 2010, H6, sw],
. . . . . . . . . . . . . . . . . . [H1N1 Avian Farm with syn346G],
. . . . . . . . 377K [H9N2],
. . . . . . . . syn388K (AAa) [Wisconsin08_30F_2010_08_10
. . . . . . . . . . . . . . . . . . . . . with 39R, 137T, 186P,
. . . . . . . . . . . . . . . . . . . . . . . . . 225N, syn346G, syn413K, 444K,
. . . . . . . . . . . . . . . . . . Utah20_C2_2_2009_07_25_VxX
. . . . . . . . . . . . . . . . . . . . . with #12E, 0I, 159D, 227G, 296H, 470I],
. . . . . . . . . . . . . . . . . . [H5N1 Avian, Equine, Human wt],
. . . . . . . . . . . . . . . . . . [H9N2 Avian and Human
. . . . . . . . . . . . . . . . . . . . . . with 39E, syn40H, syn42G, 296H],
. . . . . . . . . . . . . . . . . . [swIowa44837_1_2009_11_08_xL
. . . . . . . . . . . . . . . . . . . . . . with syn41N, 50I, 196H,
. . . . . . . . . . . . . . . . . . . . . . . . . 225N, 230I, 238D,
. . . . . . . . . . . . . . . . . . . . . . . . . syn346G, syn413K],
. . . . . . . . 415E [H5N1 Egypt wt],
. . . . . . . . 416N mix [H5N1 Avian Egypt
. . . . . . . . . . . . . . . . . . . with 100N, 196H, 415E],
. . . . . . . . 416Y mix,
. . . . . . . . 454N [H7N3, H7N7, H9N2],
. . . . . . . . syn527L (TTa) [BeijingHZ01_2011_01_14
. . . . . . . . . . . . . . . . . . . . . . . . with 188T, 242N],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt wt (cTa)]

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