2011-07-20

Arizona 2011 on a Pandemic Background with an Observed 5% Case Fatality Rate

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
2011-07-20

On 2011-06-21, the lead public health agency from the United States released 50 sequences at GISAID containing a subset from a heavily zoonotic sub-clade that is circulating across a worldwide geography in Americans and in individuals of at least 11 other nationalities.  Eight matched pairs (HA and NA segments) from the emergent sub-clade are found in this deposit.

This Pandemic H1N1 Upsilon Sub-Clade is termed as pH1N1υ for reference brevity and encompasses the 230I-Permissive, 189T-Bearing Hydra that has emerged from January 2010 to April 2011 across 62 HA and 53 NA sequences defining a clinical subset of 58 cases, including fatalities, vaccine escape situations and TamiFlu resistance.  Across the HA segments (19 Fragments), 745 polymorphisms are found (93 distinct).  The NA is less volatile, but does lead other sub-clades with 251 polymorphisms spread over 68 distinct codons. 

Although complete clinical outcomes are not forthcoming, the Case Fatality Rate for pH1N1υ cases remains at or above 5% for a number of reasons, including very high Zoonotic Potential scores indicating rapid acquisition of genetic material from animal reservoirs.  This sub-clade displays hypermorphic behaviour, carrying an average of 12 changes per HA and 4.7 per NA.  At this analysis, GeneWurx investigates the potential donor reservoirs for the late season 2011 sequence that bears the highest count of pH1N1υ HA polymorphisms, Arizona02_43F_2011_03_08.  The HA polymorphism count of 19 (7 Amino and 12 Silent) and 6 for the NA (0 Amino and 6 Silent) ranks this sequence within the ultimate decile of cladded pH1N1 sequences.

Four HA revisions novel to pH1N1υ demonstrate a continued genetic re-seeding though the base of this sub-clade is founded on a significant immune escape charge.  A triad of novelties (210N, syn334G, syn337A) are found individually and grouped on various animal reservoirs closely related to the change pattern for pH1N1υ, H2N2 and H6N1.  The fourth novelty, 516V, appears within H2N2. The 210N and syn337A have recently appeared on pH1N1 Clade 2: 188T.

Sequences

Clade 1.Upsilon:
34D, 165N, 189T, syn213F, syn305K

. . . . Arizona02_43F_2011_03_08 (
. . . . . . . . Zoonotic Potential: 100%
. . . . . . . . GISAID HA EPI319994
. . . . . . . . 19 Polymorphisms (7 Amino and 12 Silent)
. . . . . . . . syn31H (CAt) [H2N2 Human and Avian wt],
. . . . . . . . . . . . . . . . . [H2N3 with syn40H],
. . . . . . . . . . . . . . . . . [H5N1 Egypt Human 2009],
. . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2008-2009],
. . . . . . . . . . . . . . . . . [H5N1 Europe Avian 1999-2009
. . . . . . . . . . . . . . . . . . . . with 34D, syn40H, syn42G],
. . . . . . . . . . . . . . . . . [H5N1 Asia Avian 2002-2008
. . . . . . . . . . . . . . . . . . . . with 34D, syn40H, syn42G],
. . . . . . . . . . . . . . . . . [H5N1 Africa Avian 2004-2008],
. . . . . . . . . . . . . . . . . [H9N2 Avian and Human wt],
. . . . . . . . . . . . . . . . . [H1N1 Human Seasonal 1988-1989
. . . . . . . . . . . . . . . . . . . . . with 219K, 225G, 230I, syn397G],
. . . . . . . . . . . . . . . . . [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with #1T, 8V, 22I, syn42G, 72L,
. . . . . . . . . . . . . . . . . . . . . syn80S, syn82I, 87N, syn118E,
. . . . . . . . . . . . . . . . . . . . . 156E, 158E, 200T, 218V,
. . . . . . . . . . . . . . . . . . . . . syn228G, 231S,
. . . . . . . . . . . . . . . . . . . . . syn287G, syn346G,
. . . . . . . . . . . . . . . . . . . . . 450D, 453K, 502K],
. . . . . . . . . . . . . . . . . [WSN_1933],
. . . . . . . . 34D [H5N1 Egypt Human 2009-2010],
. . . . . . . . . . .  [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . .  [H5N1 Egypt Equine 2009],
. . . . . . . . . . .  [H5N1 Egypt Avian 2007-2010],
. . . . . . . . . . .  [H2N2 Human and Avian wt],
. . . . . . . . syn55L (TTa) [H5N1 Egypt Human 2009-2010],
. . . . . . . . . . . . . . . . .  [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . . . . . .  [H5N1 Azerbaijan Human 2006],
. . . . . . . . . . . . . . . . .  [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . .  [H5N1 Egypt Avian 2007-2010],
. . . . . . . . . . . . . . . . .  [H5N1 Feline with syn40H, syn469E],
. . . . . . . . . . . . . . . . .  [H2N2 Avian with syn184H, 189T],
. . . . . . . . . . . . . . . . .  [H2N2 Human and Avian (cTa)],
. . . . . . . . syn118E (GAa) [H3N8 Equine wt, Canine wt, Swine wt],
. . . . . . . . . . . . . . . . . . [H3N8 Avian],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2009-2010 (cAa):
. . . . . . . . . . . . . . . . . . . . . . ckEgypt1055_2010_02,
. . . . . . . . . . . . . . . . . . . . . . dkEgypt0972NLQP_2009_04],
. . . . . . . . . . . . . . . . . . [H4, H6N1],
. . . . . . . . . . . . . . . . . . [H1N1 Human Seasonal wt],
. . . . . . . . . . . . . . . . . . [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with #1T, 8V, 22I, syn31H,
. . . . . . . . . . . . . . . . . . . . . . . . syn40H, syn42G, 72L,
. . . . . . . . . . . . . . . . . . . . . . . . syn80S, syn81Y, syn82I, 87N,
. . . . . . . . . . . . . . . . . . . . . . . . 144K, 156E, 158E, 158N, 159G,
. . . . . . . . . . . . . . . . . . . . . . . . 200T, 218S, 218V,
. . . . . . . . . . . . . . . . . . . . . . . . syn228G, 230I, 231S,
. . . . . . . . . . . . . . . . . . . . . . . . 275I, syn287G, 313I, syn346G,
. . . . . . . . . . . . . . . . . . . . . . . . 450D, 453K, 502K, 523A, 523I],
. . . . . . . . . . . . . . . . . . [S8, 1918],
. . . . . . . . . . . . . . . . . . [WSN_1933, WSZ_1933],
. . . . . . . . . . . . . . . . . . [swBelgium1_1998],
. . . . . . . . syn140P (CCa) [H5N1 Egypt Human 2007-2010],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
. . . . . . . . 149N [H3N8 Equine, Canine, Avian, Swine (Agc)],
. . . . . . . . . . . . [H3N2 Avian (Agc)
. . . . . . . . . . . . . . . . with 165N, 190E,
. . . . . . . . . . . . . . . . . . . 225G, 230I, 238K, 275I],
. . . . . . . . . . . . [H3N2 Avian (cgc)],
. . . . . . . . . . . . [H4 Avian],
. . . . . . . . 165N [H6N1 Avian
. . . . . . . . . . . . . . . . with 188T, 225G, 230I, 275I,
. . . . . . . . . . . . . . . . . . syn334G, syn346G, 377K, syn390N,
. . . . . . . . . . . . . . . . . . syn399E, 453K, 502K],
. . . . . . . . . . . . [H9N2 Avian Emergent
. . . . . . . . . . . . . . . . with 39E, syn40H, syn93C,
. . . . . . . . . . . . . . . . . . . syn181G, 189T, 190E,
. . . . . . . . . . . . . . . . . . . 225G, 230I,
. . . . . . . . . . . . . . . . . . . syn294P, 296H, syn404E],
. . . . . . . . . . . . [H10N7 Avian 2008
. . . . . . . . . . . . . . . . . with #1V, 87N, syn94Y, 100N, syn102E,
. . . . . . . . . . . . . . . . . . . 156E, 157E, 163T, 165N, syn177L,
. . . . . . . . . . . . . . . . . . . 188T, syn207S, syn213F, syn221P,
. . . . . . . . . . . . . . . . . . . 225G, 230I, 233H, 237I, syn239P,
. . . . . . . . . . . . . . . . . . . syn338G, syn346G, syn356H,
. . . . . . . . . . . . . . . . . . . syn390N, syn391T],
. . . . . . . . . . . . [H3N2 Human with 225N, 230I],
. . . . . . . . . . . . [H3N2 Avian, Canine, Feline, Mink
. . . . . . . . . . . . . . . . with 225G, 230I],
. . . . . . . . . . . . [WSZ_1933],
. . . . . . . . 189T [H3N2 Human (aaa, aag, agg)]
. . . . . . . . . . . . [H5N1 Egypt Human 2009-2010],
. . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . [H5N1 Egypt Avian 2007-2009],
. . . . . . . . . . . . [H6N1 Avian
. . . . . . . . . . . . . . . . with 165K, 188T, 225G, 230I,
. . . . . . . . . . . . . . . . . . 275I, syn334G, syn346G, syn390N,
. . . . . . . . . . . . . . . . . . syn399E, 453K, 502K],
. . . . . . . . . . . . [H9N2 Avian
. . . . . . . . . . . . . . . . with 39E, syn40H, syn42G, syn93C,
. . . . . . . . . . . . . . . . . . . syn181G, 189T, 190E,
. . . . . . . . . . . . . . . . . . . 225G, 230I, syn294P, 296H,
. . . . . . . . . . . . . . . . . . . syn399E, syn404E, 453K, 502K],
. . . . . . . . . . . . [H9N2 Human
. . . . . . . . . . . . . . . . with 189T, 190E,
. . . . . . . . . . . . . . . . . . . 225G, 230I, syn294P, 296H,
. . . . . . . . . . . . . . . . . . . syn399E, 453K, 502K],
. . . . . . . . . . . . [H1N1 Avian Europe 2009
. . . . . . . . . . . . . . . . with #1T, syn42G, 72L, syn81Y, syn82I, 87N,
. . . . . . . . . . . . . . . . . . . 159T, 186P, 188T, syn346G],
. . . . . . . . . . . . [H1N1 Avian Farm
. . . . . . . . . . . . . . . . with #1T, syn40H, syn42G,
. . . . . . . . . . . . . . . . . . . 72L, syn80S, syn81Y, 87N
. . . . . . . . . . . . . . . . . . . 144E, 158E, 186P,
. . . . . . . . . . . . . . . . . . . 230I, 237I, syn346G, 523A],
. . . . . . . . . . . . [H2N2 Human, Avian
. . . . . . . . . . . . . . . . with 200T, 208K, 225E,
. . . . . . . . . . . . . . . . . . 225G, 238D, 238K, 253A],
. . . . . . . . . . . . [1918 with 186P, 208K, 219A, 225G, 252I],
. . . . . . . . 210N mix wt [Novel to pH1N1υ],
. . . . . . . . . . . . . . . . .  [pH1N1 Clade 2: 188T with 128D],
. . . . . . . . . . . . . . . . .  [H1N1 Avian wt],
. . . . . . . . . . . . . . . . .  [H2N2 Human],
. . . . . . . . . . . . . . . . .  [H2N2 Avian
. . . . . . . . . . . . . . . . . . . . . . with syn#1A, syn31H, 42E, syn147F,
. . . . . . . . . . . . . . . . . . . . . . . . . .188A, 189T, 190E, 200T,
. . . . . . . . . . . . . . . . . . . . . . . . . .210N, 225G, syn228G,
. . . . . . . . . . . . . . . . . . . . . . . . .  238K, 240N, syn346G],
. . . . . . . . . . . . . . . . .  [H6N1 Avian wt],
. . . . . . . . . . . . . . . . . .[1918, WSN_1933, WSZ_1933],
. . . . . . . . syn213F (TTt) [H5N1, H7N3, H7N7, H9N2],
. . . . . . . . . . . . . . . . .  [H10N7 Avian 2008
. . . . . . . . . . . . . . . . . . . . . . with 87N, 100N, syn102E,
. . . . . . . . . . . . . . . . . . . . . . . . 156E, 157E, 163T, 165N,
. . . . . . . . . . . . . . . . . . . . . . . . syn177L, 188T, syn221P, syn207S, syn213F,
. . . . . . . . . . . . . . . . . . . . . . . . 225G, 230I, 233H, 237I, syn239P,
. . . . . . . . . . . . . . . . . . . . . . . . syn338G, syn346G, syn356H,
. . . . . . . . . . . . . . . . . . . . . . . . syn390N, syn391T],
. . . . . . . . . . . . . . . . .  [H1N1 Avian],
. . . . . . . . 275I [H6N1 Avian wt],
. . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . . . . . [H3N2 Human 2011
. . . . . . . . . . . . . . . . with 165N, 225N, 230I, 238K],
. . . . . . . . . . . . [H3N2 Avian, Canine, Feline
. . . . . . . . . . . . . . . . with 165N, 190E, 225G, 230I, 238K],
. . . . . . . . syn287G (GGg) [H3N2 Avian with 159S],
. . . . . . . . . . . . . . . . . . [H3N2 Canine & Feline],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human 2007-2010],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2008-2010],
. . . . . . . . . . . . . . . . . . [H1N1 Avian wt],
. . . . . . . . . . . . . . . . . . [H2N2 Avian
. . . . . . . . . . . . . . . . . . . . . . with syn31H, 42E, syn104L,
. . . . . . . . . . . . . . . . . . . . . . . . . 166R, syn184H,
. . . . . . . . . . . . . . . . . . . . . . . . . 189T, 225G, 238K, syn346G]
. . . . . . . . . . . . . . . . . . [H2N2 Human
. . . . . . . . . . . . . . . . . . . . . . with 42E, 189T, 225G, 238D, 253A],
. . . . . . . . . . . . . . . . . . [swBelgium1_1998],
. . . . . . . . syn305K (AAg) [H2N2 Avian & Human (gAg)],
. . . . . . . . . . . . . . . . . . [H2N3 Avian wt],
. . . . . . . . . . . . . . . . . . [H3N8 Avian (gcg)],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Gharbiyah/Qena Avian 2008 (AAa)],
. . . . . . . . . . . . . . . . . . [H5N1 Human VietJP4207_2005 (gAg)],
. . . . . . . . . . . . . . . . . . [H5N1 Asia Avian 2001-2006 (gAg)],
. . . . . . . . . . . . . . . . . . [H7N3, H7N7],
. . . . . . . . . . . . . . . . . . [H1N1 Avian (gAg)],
. . . . . . . . . . . . . . . . . . [H1N1 Human Seasonal wt (gAg)
. . . . . . . . . . . . . . . . . . . . . . . with syn12A, syn42G, 48K, syn84E,
. . . . . . . . . . . . . . . . . . . . . . . . . . syn218A, 218T, 218S,
. . . . . . . . . . . . . . . . . . . . . . . . . . 219K, 225G, 230I,
. . . . . . . . . . . . . . . . . . . . . . . . . . syn397G, syn494E],
. . . . . . . . . . . . . . . . . . [H1N1 swine
. . . . . . . . . . . . . . . . . . . . . . . with #1S, 219K, 225G, 230I, 491R],
. . . . . . . . . . . . . . . . . . [1918 (gAg)],
. . . . . . . . . . . . . . . . . . [WSN_1933, WSZ_1933 (gAg)],
. . . . . . . . syn334G (GGa) [Novel to pH1N1υ],
. . . . . . . . . . . . . . . . . . [H1N1 Avian wt],
. . . . . . . . . . . . . . . . . . [H2N2 Avian
. . . . . . . . . . . . . . . . . . . . . . with syn31H, 42E,
. . . . . . . . . . . . . . . . . . . . . . . . . . 189T, 200T, 208K, 210N,
. . . . . . . . . . . . . . . . . . . . . . . . . . 225G, 238K, syn287G, syn346G],
. . . . . . . . . . . . . . . . . . [H6N1 Avian wt],
. . . . . . . . . . . . . . . . . . [H10N7 Avian wt
. . . . . . . . . . . . . . . . . . . . . . . with 156E, syn213F, syn346G, et al],
. . . . . . . . . . . . . . . . . . [1918, WSN_1933, WSZ_1933],
. . . . . . . . syn337A (GCa) [Novel to pH1N1υ],
. . . . . . . . . . . . . . . . . . [pH1N1 Clade 2: 188T with 158E],
. . . . . . . . . . . . . . . . . . [H2N2 Avian
. . . . . . . . . . . . . . . . . . . . . . . with syn#1A, syn31H, syn147F, 166R
. . . . . . . . . . . . . . . . . . . . . . . . . . 188A, 190E, 200T,
. . . . . . . . . . . . . . . . . . . . . . . . . . 210N, 225G, syn228G,
. . . . . . . . . . . . . . . . . . . . . . . . . . 238K, 240N, syn346G],
. . . . . . . . . . . . . . . . . .  [H6N1 Avian wt],
. . . . . . . . syn346G (GGa) [H2N2 Human and Avian wt],
. . . . . . . . . . . . . . . . . . [H3N2 Human & Avian wt],
. . . . . . . . . . . . . . . . . . [H3N8],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Preschool 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
. . . . . . . . . . . . . . . . . . [H6N1, H6N2, H6N4 Avian],
. . . . . . . . . . . . . . . . . . [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],
. . . . . . . . . . . . . . . . . . [S8, 1918], [swBelgium1_1998],
. . . . . . . . syn391T (ACg) [H3N2 Human wt (gag)],
. . . . . . . . . . . . . . . . . . [H3N2 Avian, Canine, Feline (gag)],
. . . . . . . . . . . . . . . . . . [H4 Avian wt (gag)],
. . . . . . . . . . . . . . . . . . [H7N3 Avian wt (cag)],
. . . . . . . . . . . . . . . . . . [H7N7 Avian, Equine, Marine Mammal (cag)],
. . . . . . . . . . . . . . . . . . [H9N2 Human 2009 (Aag)],
. . . . . . . . . . . . . . . . . . [H9N2 Avian 2011 (Aag)],
. . . . . . . . . . . . . . . . . . [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],
. . . . . . . . . . . . . . . . . . [H11 Avian extensive],
. . . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . syn397G (GGc) [H6N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with 165N, syn181G, 188T, 190E,
. . . . . . . . . . . . . . . . . . . . . . . . . . 210N, 225G, 230I, 275I,
. . . . . . . . . . . . . . . . . . . . . . . . . . 313K, syn334G, syn337A, 377K,
. . . . . . . . . . . . . . . . . . . . . . . . . . syn390N, syn399E, 453K, 502K],
. . . . . . . . . . . . . . . . . . [H7N3 Avian (Gac)],
. . . . . . . . . . . . . . . . . . [H7N7 Human & Avian (Gac)],
. . . . . . . . . . . . . . . . . . [H9N2 Human (Gac)],
. . . . . . . . . . . . . . . . . . [H9N2 Avian Emergent (Gac)
. . . . . . . . . . . . . . . . . . . . . . . with 39E, syn40H, 296H, syn404E],
. . . . . . . . . . . . . . . . . . [H1N1 Human Seasonal wt
. . . . . . . . . . . . . . . . . . . . . . . with syn12A, syn42G, 48K, syn84E,
. . . . . . . . . . . . . . . . . . . . . . . . . syn218A, 218T, 218S,
. . . . . . . . . . . . . . . . . . . . . . . . . 219K, syn220R, 225G, 230I,
. . . . . . . . . . . . . . . . . . . . . . . . . syn494E],
. . . . . . . . . . . . . . . . . . [H1N1 Avian 2009],
. . . . . . . . . . . . . . . . . . [S8], [swBelgium1_1998],
. . . . . . . . 516V [Novel to pH1N1υ],
. . . . . . . . . . . . [H2N2 Avian with 17N])

. . . . Arizona02_43F_2011_03_08 (
. . . . . . . . GISAID NA EPI319993
. . . . . . . . 6 Polymorphisms (0 Amino and 6 Silent)
. . . . . . . . syn20A (GCc),
. . . . . . . . syn139L (TTa),
. . . . . . . . syn300N (AAc),
. . . . . . . . syn327R (CGt),
. . . . . . . . syn330D (GAc),
. . . . . . . . syn453V (GTt))




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