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.
1. Hurt AC, Lee RT, Leang SK, Cui L, Deng YM, Phuah SP, Caldwell N, Freeman K, Komadina N, Smith D, Speers D, Kelso A, Lin RT, Maurer-Stroh S, Barr IG. Increased detection in Australia and Singapore of a novel influenza A(H1N1)2009 variant with reduced oseltamivir and zanamivir sensitivity due to a S247N neuraminidase mutation. Euro Surveill. 2011;16(23):pii=19884.
Available online: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19884
Date of submission: 26 May 2011
“A novel influenza A(H1N1)2009 variant with mildly reduced oseltamivir and zanamivir sensitivity has been detected in more than 10% of community specimens in Singapore and more than 30% of samples from northern Australia during the early months of 2011.”1
Last Updated
2011-06-16
On 2011-06-02, the WHO Collaborating Centre for Reference and Research on Influenza published 10 HA and 12 NA pH1N1 sequence segments at GISAID in support of their paper 1 on the MultiDrug Resistance moderated by NA 247N. These sequences were sampled from patients in Australia and Brunei from January to March 2011. In addition to the discussed NA 247N, all 12 Neuraminidase segments display multiple polymorphism recombination at the 5’ end with a zoonotic co-infection from a strain matching Human and Avian H5N1 cases as well as H4, H6, H9N2, H10, H11, H12 and H13 sequences. The Brunei sequence exhibits potential recombination to the same zoonotic reservoirs with additional NA nucleotide homology at aa40, aa46, aa95, 157T, aa353, 369K, aa377 and aa426.
These sequences are deeply avian in nature with additional homology to various zoonotic reservoirs. Though the primary subclade carrying this drug resistance marker is young, the basic backbone has risen to triple digits rather quickly. The HA and the NA segments in this deposit represent hypermorphic outcomes signaling a change in viral behaviour on SubClade 5 (208K_219V) in this region of the world during early 2011. Notice must be made that the NA 247N has crossed onto the HA 188T SubClade as well. Existence of the newly recognised TamiFlu resistance marker across multiple human pandemic subclades indicates potential for spread.
As we have previously discussed concerning genetic markers for drug resistance, GeneWurx expects standing genetic revisions on the pH1N1 subclades to eventually be laboratory validated for drug resistance.
. . . . AustraliaDarwin75_27F_2011_03_17 (
. . . . . . . . GISAID HA EPI319199
. . . . . . . . 17 Polymorphisms (8 Amino and 9 Silent)
. . . . . . . . syn47L (CTg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . syn82I (ATc) [H5N1 Human (ATa)],
. . . . . . . . syn93C (TGc),
. . . . . . . . 100N [H1N1 Avian
. . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 141Q,
. . . . . . . . syn170N (AAc) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 208K [H1N1 Avian
. . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 219V,
. . . . . . . . 252L,
. . . . . . . . 262K [H5N1 Human (Aag)],
. . . . . . . . syn307P (CCc) [H5N1 Bangladesh Human 2011],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human 2007-2010 with Fatalities],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
. . . . . . . . . . . . . . . . . . [H5N1 Cambodia Human 2005],
. . . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . 359A,
. . . . . . . . 377K,
. . . . . . . . syn408E (GAa) [H2N3 Avian],
. . . . . . . . . . . . . . . . . . [H5N1 Bangladesh Human 2011],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human 2007-2010 with Fatalities],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
. . . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . . . . . . . . . . . [WSN_1933],
. . . . . . . . . . . . . . . . . . [WSZ_1933],
. . . . . . . . . . . . . . . . . . [1918],
. . . . . . . . syn446K (AAa) [WSZ_1933],
. . . . . . . . syn475D (GAc) [H5N1 Egypt Human 2009 with 196H],
. . . . . . . . . . . . . . . . . . [WSN_1933],
. . . . . . . . . . . . . . . . . . [WSZ_1933],
. . . . . . . . . . . . . . . . . . [1918],
. . . . . . . . syn549R (AGg))
. . . . AustraliaDarwin75_27F_2011_03_17 (
. . . . . . . . GISAID NA EPI319198
. . . . . . . . 12 Polymorphisms (4 Amino and 8 Silent)
. . . . . . . . syn4N (AAt) [H5N1 Avian and Human],
. . . . . . . . syn5Q (CAg) [H5N1 Avian and Human],
. . . . . . . . syn89S (TCt) [H1N1 Avian],
. . . . . . . . syn126P (CCt) [H6N2 Avian],
. . . . . . . . . . . . . . . . . . [H1N1 Avian (Cat)],
. . . . . . . . syn229S (TCc) [H1N1 Avian],
. . . . . . . . syn236G (GGc) [H1N1 Avian],
. . . . . . . . syn241V (GTg) [H1N1 Avian],
. . . . . . . . 247N,
. . . . . . . . syn268E (GAg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 299A,
. . . . . . . . 466R,
. . . . . . . . 467S)
. . . . AustraliaDarwin75_MDCK1_27F_2011_03_17 (
. . . . . . . . GISAID HA EPI319166
. . . . . . . . 15 Polymorphisms (8 Amino and 7 Silent)
. . . . . . . . syn47L (CTg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . syn82I (ATc) [H5N1 Human (ATa)],
. . . . . . . . syn93C (TGc),
. . . . . . . . 100N [H1N1 Avian
. . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 141Q,
. . . . . . . . syn170N (AAc) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 208K [H1N1 Avian
. . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 219V,
. . . . . . . . 252L,
. . . . . . . . 262K [H5N1 Human (Aag)],
. . . . . . . . syn307P (CCc) [H5N1 Bangladesh Human 2011],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human 2007-2010 with Fatalities],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
. . . . . . . . . . . . . . . . . . [H5N1 Cambodia Human 2005],
. . . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . 359A,
. . . . . . . . 377K,
. . . . . . . . syn408E (GAa) [H2N3 Avian],
. . . . . . . . . . . . . . . . . . [H5N1 Bangladesh Human 2011],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human 2007-2010 with Fatalities],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
. . . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . . . . . . . . . . . [WSN_1933],
. . . . . . . . . . . . . . . . . . [WSZ_1933],
. . . . . . . . . . . . . . . . . . [1918],
. . . . . . . . syn446K (AAa) [WSZ_1933])
. . . . AustraliaDarwin75_MDCK1_27F_2011_03_17 (
. . . . . . . . GISAID NA EPI319165
. . . . . . . . 10 Polymorphisms (2 Amino and 8 Silent)
. . . . . . . . syn4N (AAt) [H5N1 Avian and Human],
. . . . . . . . syn5Q (CAg)) [H5N1 Avian and Human],
. . . . . . . . syn89S (TCt) [H1N1 Avian],
. . . . . . . . syn126P (CCt) [H6N2 Avian],
. . . . . . . . . . . . . . . . . . [H1N1 Avian (Cat)],
. . . . . . . . syn229S (TCc) [H1N1 Avian],
. . . . . . . . syn236G (GGc) [H1N1 Avian],
. . . . . . . . syn241V (GTg) [H1N1 Avian],
. . . . . . . . 247N,
. . . . . . . . syn268E (GAg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 299A)
. . . . AustraliaDarwin74_17F_2011_03_16 (
. . . . . . . . GISAID HA EPI319170
. . . . . . . . 17 Polymorphisms (8 Amino and 9 Silent)
. . . . . . . . syn47L (CTg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . syn82I (ATc) [H5N1 Human (ATa)],
. . . . . . . . syn93C (TGc),
. . . . . . . . 100N [H1N1 Avian
. . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 141Q,
. . . . . . . . syn170N (AAc) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 208K [H1N1 Avian
. . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 219V,
. . . . . . . . 252L,
. . . . . . . . syn307P (CCc) [H5N1 Bangladesh Human 2011],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human 2007-2010 with Fatalities],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
. . . . . . . . . . . . . . . . . . [H5N1 Cambodia Human 2005],
. . . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . 359A,
. . . . . . . . 377K,
. . . . . . . . syn408E (GAa) [H2N3 Avian],
. . . . . . . . . . . . . . . . . . [H5N1 Bangladesh Human 2011],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human 2007-2010 with Fatalities],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
. . . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . . . . . . . . . . . [WSN_1933],
. . . . . . . . . . . . . . . . . . [WSZ_1933],
. . . . . . . . . . . . . . . . . . [1918],
. . . . . . . . syn446K (AAa) [WSZ_1933],
. . . . . . . . syn475D (GAc) [H5N1 Egypt Human 2009 with 196H],
. . . . . . . . . . . . . . . . . . [WSN_1933],
. . . . . . . . . . . . . . . . . . [WSZ_1933],
. . . . . . . . . . . . . . . . . . [1918],
. . . . . . . . syn549R (AGg),
. . . . . . . . 550S)
. . . . AustraliaDarwin74_17F_2011_03_16 (
. . . . . . . . GISAID NA EPI319169
. . . . . . . . 10 Polymorphisms (2 Amino and 8 Silent)
. . . . . . . . syn4N (AAt) [H5N1 Avian and Human],
. . . . . . . . syn5Q (CAg)) [H5N1 Avian and Human],
. . . . . . . . syn89S (TCt) [H1N1 Avian],
. . . . . . . . syn126P (CCt) [H6N2 Avian],
. . . . . . . . . . . . . . . . . . [H1N1 Avian (Cat)],
. . . . . . . . syn229S (TCc) [H1N1 Avian],
. . . . . . . . syn236G (GGc) [H1N1 Avian],
. . . . . . . . syn241V (GTg) [H1N1 Avian],
. . . . . . . . 247N,
. . . . . . . . syn268E (GAg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 299A)
. . . . AustraliaDarwin74_MDCK1_17F_2011_03_16 (
. . . . . . . . GISAID HA EPI319182
. . . . . . . . 14 Polymorphisms (6 Amino and 8 Silent)
. . . . . . . . syn47L (CTg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . syn82I (ATc) [H5N1 Human (ATa)],
. . . . . . . . syn93C (TGc),
. . . . . . . . 100N [H1N1 Avian
. . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 141Q,
. . . . . . . . syn170N (AAc) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 208K [H1N1 Avian
. . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 219V,
. . . . . . . . 252L,
. . . . . . . . syn307P (CCc) [H5N1 Bangladesh Human 2011],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human 2007-2010 with Fatalities],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
. . . . . . . . . . . . . . . . . . [H5N1 Cambodia Human 2005],
. . . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . 377K,
. . . . . . . . syn408E (GAa) [H2N3 Avian],
. . . . . . . . . . . . . . . . . . [H5N1 Bangladesh Human 2011],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human 2007-2010 with Fatalities],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
. . . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . . . . . . . . . . . [WSN_1933],
. . . . . . . . . . . . . . . . . . [WSZ_1933],
. . . . . . . . . . . . . . . . . . [1918],
. . . . . . . . syn446K (AAa) [WSZ_1933],
. . . . . . . . syn475D (GAc) [H5N1 Egypt Human 2009 with 196H],
. . . . . . . . . . . . . . . . . . [WSN_1933],
. . . . . . . . . . . . . . . . . . [WSZ_1933],
. . . . . . . . . . . . . . . . . . [1918])
. . . . AustraliaDarwin74_MDCK1_17F_2011_03_16 (
. . . . . . . . GISAID NA EPI319181
. . . . . . . . 10 Polymorphisms (2 Amino and 8 Silent)
. . . . . . . . syn4N (AAt) [H5N1 Avian and Human],
. . . . . . . . syn5Q (CAg) [H5N1 Avian and Human],
. . . . . . . . syn89S (TCt) [H1N1 Avian],
. . . . . . . . syn126P (CCt) [H6N2 Avian],
. . . . . . . . . . . . . . . . . . [H1N1 Avian (Cat)],
. . . . . . . . syn229S (TCc) [H1N1 Avian],
. . . . . . . . syn236G (GGc) [H1N1 Avian],
. . . . . . . . syn241V (GTg) [H1N1 Avian],
. . . . . . . . 247N,
. . . . . . . . syn268E (GAg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 299A)
. . . . AustraliaPerth29_40M_2011_03_08_TmX_f (
. . . . . . . . GISAID HA EPI319176
. . . . . . . . 16 Polymorphisms (8 Amino and 8 Silent)
. . . . . . . . syn47L (CTg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . syn82I (ATc) [H5N1 Human (ATa)],
. . . . . . . . syn93C (TGc),
. . . . . . . . 100N [H1N1 Avian
. . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 141Q,
. . . . . . . . syn170N (AAc) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 208K [H1N1 Avian
. . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 219V,
. . . . . . . . 252L,
. . . . . . . . 259V,
. . . . . . . . syn307P (CCc) [H5N1 Bangladesh Human 2011],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human 2007-2010 with Fatalities],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
. . . . . . . . . . . . . . . . . . [H5N1 Cambodia Human 2005],
. . . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . 359A,
. . . . . . . . 377K,
. . . . . . . . syn408E (GAa) [H2N3 Avian],
. . . . . . . . . . . . . . . . . . [H5N1 Bangladesh Human 2011],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human 2007-2010 with Fatalities],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
. . . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . . . . . . . . . . . [WSN_1933],
. . . . . . . . . . . . . . . . . . [WSZ_1933],
. . . . . . . . . . . . . . . . . . [1918],
. . . . . . . . syn446K (AAa) [WSZ_1933],
. . . . . . . . syn475D (GAc) [H5N1 Egypt Human 2009 with 196H],
. . . . . . . . . . . . . . . . . . [WSN_1933],
. . . . . . . . . . . . . . . . . . [WSZ_1933],
. . . . . . . . . . . . . . . . . . [1918])
. . . . AustraliaPerth29_40M_2011_03_08_TmX_f (
. . . . . . . . GISAID NA EPI319175
. . . . . . . . 11 Polymorphisms (3 Amino and 8 Silent)
. . . . . . . . syn4N (AAt) [H5N1 Avian and Human],
. . . . . . . . syn5Q (CAg)) [H5N1 Avian and Human],
. . . . . . . . syn89S (TCt) [H1N1 Avian],
. . . . . . . . syn126P (CCt) [H6N2 Avian],
. . . . . . . . . . . . . . . . . . [H1N1 Avian (Cat)],
. . . . . . . . syn229S (TCc) [H1N1 Avian],
. . . . . . . . syn236G (GGc) [H1N1 Avian],
. . . . . . . . syn241V (GTg) [H1N1 Avian],
. . . . . . . . 247N,
. . . . . . . . syn268E (GAg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 299A)
. . . . AustraliaDarwin54_26M_2011_03_06 (
. . . . . . . . GISAID NA EPI319184
. . . . . . . . 9 Polymorphisms (1 Amino and 8 Silent)
. . . . . . . . syn4N (AAt) [H5N1 Avian and Human],
. . . . . . . . syn5Q (CAg) [H5N1 Avian and Human],
. . . . . . . . syn89S (TCt) [H1N1 Avian],
. . . . . . . . syn126P (CCt) [H6N2 Avian],
. . . . . . . . . . . . . . . . . . [H1N1 Avian (Cat)],
. . . . . . . . syn229S (TCc) [H1N1 Avian],
. . . . . . . . syn236G (GGc) [H1N1 Avian],
. . . . . . . . syn241V (GTg) [H1N1 Avian],
. . . . . . . . 247N,
. . . . . . . . syn268E (GAg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms])
. . . . AustraliaPerth30_40M_2011_03_01_f (
. . . . . . . . GISAID HA EPI319178
. . . . . . . . 16 Polymorphisms (8 Amino and 8 Silent)
. . . . . . . . syn47L (CTg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . syn82I (ATc) [H5N1 Human (ATa)],
. . . . . . . . syn93C (TGc),
. . . . . . . . 100N [H1N1 Avian
. . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 141Q,
. . . . . . . . syn170N (AAc) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 208K [H1N1 Avian
. . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 219V,
. . . . . . . . 252L,
. . . . . . . . 259V,
. . . . . . . . syn307P (CCc) [H5N1 Bangladesh Human 2011],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human 2007-2010 with Fatalities],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
. . . . . . . . . . . . . . . . . . [H5N1 Cambodia Human 2005],
. . . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . 359A,
. . . . . . . . 377K,
. . . . . . . . syn408E (GAa) [H2N3 Avian],
. . . . . . . . . . . . . . . . . . [H5N1 Bangladesh Human 2011],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human 2007-2010 with Fatalities],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
. . . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . . . . . . . . . . . [WSN_1933],
. . . . . . . . . . . . . . . . . . [WSZ_1933],
. . . . . . . . . . . . . . . . . . [1918],
. . . . . . . . syn446K (AAa) [WSZ_1933],
. . . . . . . . syn475D (GAc) [H5N1 Egypt Human 2009 with 196H],
. . . . . . . . . . . . . . . . . . [WSN_1933],
. . . . . . . . . . . . . . . . . . [WSZ_1933],
. . . . . . . . . . . . . . . . . . [1918])
. . . . AustraliaPerth30_40M_2011_03_01_f (
. . . . . . . . GISAID NA EPI319177
. . . . . . . . 10 Polymorphisms (2 Amino and 8 Silent)
. . . . . . . . syn4N (AAt) [H5N1 Avian and Human],
. . . . . . . . syn5Q (CAg)) [H5N1 Avian and Human],
. . . . . . . . syn89S (TCt) [H1N1 Avian],
. . . . . . . . syn126P (CCt) [H6N2 Avian],
. . . . . . . . . . . . . . . . . . [H1N1 Avian (Cat)],
. . . . . . . . syn229S (TCc) [H1N1 Avian],
. . . . . . . . syn236G (GGc) [H1N1 Avian],
. . . . . . . . syn241V (GTg) [H1N1 Avian],
. . . . . . . . 247N,
. . . . . . . . syn268E (GAg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 299A)
. . . . AustraliaDarwin70_20F_2011_02_14 (
. . . . . . . . GISAID HA EPI319174
. . . . . . . . 15 Polymorphisms (7 Amino and 8 Silent)
. . . . . . . . syn47L (CTg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . syn82I (ATc) [H5N1 Human (ATa)],
. . . . . . . . syn93C (TGc),
. . . . . . . . 100N [H1N1 Avian
. . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 141Q,
. . . . . . . . syn170N (AAc) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 208K [H1N1 Avian
. . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 219V,
. . . . . . . . 252L,
. . . . . . . . syn307P (CCc) [H5N1 Bangladesh Human 2011],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human 2007-2010 with Fatalities],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
. . . . . . . . . . . . . . . . . . [H5N1 Cambodia Human 2005],
. . . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . 359A,
. . . . . . . . 377K,
. . . . . . . . syn408E (GAa) [H2N3 Avian],
. . . . . . . . . . . . . . . . . . [H5N1 Bangladesh Human 2011],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human 2007-2010 with Fatalities],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
. . . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . . . . . . . . . . . [WSN_1933],
. . . . . . . . . . . . . . . . . . [WSZ_1933],
. . . . . . . . . . . . . . . . . . [1918],
. . . . . . . . syn446K (AAa) [WSZ_1933],
. . . . . . . . syn475D (GAc) [H5N1 Egypt Human 2009 with 196H],
. . . . . . . . . . . . . . . . . . [WSN_1933],
. . . . . . . . . . . . . . . . . . [WSZ_1933],
. . . . . . . . . . . . . . . . . . [1918])
. . . . AustraliaDarwin70_20F_2011_02_14 (
. . . . . . . . GISAID NA EPI319173
. . . . . . . . 11 Polymorphisms (3 Amino and 8 Silent)
. . . . . . . . syn4N (AAt) [H5N1 Avian and Human],
. . . . . . . . syn5Q (CAg)) [H5N1 Avian and Human],
. . . . . . . . syn89S (TCt) [H1N1 Avian],
. . . . . . . . syn126P (CCt) [H6N2 Avian],
. . . . . . . . . . . . . . . . . . [H1N1 Avian (Cat)],
. . . . . . . . syn229S (TCc) [H1N1 Avian],
. . . . . . . . syn236G (GGc) [H1N1 Avian],
. . . . . . . . syn241V (GTg) [H1N1 Avian],
. . . . . . . . 247N,
. . . . . . . . syn268E (GAg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 299A,
. . . . . . . . 466R)
. . . . AustraliaDarwin11_27F_2011_02_11 (
. . . . . . . . GISAID NA EPI319183
. . . . . . . . 11 Polymorphisms (2 Amino and 9 Silent)
. . . . . . . . syn4N (AAt) [H5N1 Avian and Human],
. . . . . . . . syn5Q (CAg)) [H5N1 Avian and Human],
. . . . . . . . syn89S (TCt) [H1N1 Avian],
. . . . . . . . syn126P (CCt) [H6N2 Avian],
. . . . . . . . . . . . . . . . . . [H1N1 Avian (Cat)],
. . . . . . . . syn229S (TCc) [H1N1 Avian],
. . . . . . . . syn236G (GGc) [H1N1 Avian],
. . . . . . . . syn241V (GTg) [H1N1 Avian],
. . . . . . . . 247N,
. . . . . . . . syn268E (GAg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 299A,
. . . . . . . . syn433E (GAa) [H3N1 Swine],
. . . . . . . . . . . . . . . . . . [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms])
. . . . AustraliaDarwin10_37M_2011_02_09 (
. . . . . . . . GISAID HA EPI319172
. . . . . . . . 15 Polymorphisms (7 Amino and 8 Silent)
. . . . . . . . syn47L (CTg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . syn82I (ATc) [H5N1 Human (ATa)],
. . . . . . . . syn93C (TGc),
. . . . . . . . 100N [H1N1 Avian
. . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 141Q,
. . . . . . . . syn170N (AAc) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 208K [H1N1 Avian
. . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 219V,
. . . . . . . . 252L,
. . . . . . . . syn307P (CCc) [H5N1 Bangladesh Human 2011],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human 2007-2010 with Fatalities],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
. . . . . . . . . . . . . . . . . . [H5N1 Cambodia Human 2005],
. . . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . 359A,
. . . . . . . . 377K,
. . . . . . . . syn408E (GAa) [H2N3 Avian],
. . . . . . . . . . . . . . . . . . [H5N1 Bangladesh Human 2011],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human 2007-2010 with Fatalities],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
. . . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . . . . . . . . . . . [WSN_1933],
. . . . . . . . . . . . . . . . . . [WSZ_1933],
. . . . . . . . . . . . . . . . . . [1918],
. . . . . . . . syn446K (AAa) [WSZ_1933],
. . . . . . . . syn475D (GAc) [H5N1 Egypt Human 2009 with 196H],
. . . . . . . . . . . . . . . . . . [WSN_1933],
. . . . . . . . . . . . . . . . . . [WSZ_1933],
. . . . . . . . . . . . . . . . . . [1918])
. . . . AustraliaDarwin10_37M_2011_02_09 (
. . . . . . . . GISAID NA EPI319171
. . . . . . . . 10 Polymorphisms (2 Amino and 8 Silent)
. . . . . . . . syn4N (AAt) [H5N1 Avian and Human],
. . . . . . . . syn5Q (CAg)) [H5N1 Avian and Human],
. . . . . . . . syn89S (TCt) [H1N1 Avian],
. . . . . . . . syn126P (CCt) [H6N2 Avian],
. . . . . . . . . . . . . . . . . . [H1N1 Avian (Cat)],
. . . . . . . . syn229S (TCc) [H1N1 Avian],
. . . . . . . . syn236G (GGc) [H1N1 Avian],
. . . . . . . . syn241V (GTg) [H1N1 Avian],
. . . . . . . . 247N,
. . . . . . . . syn268E (GAg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 299A)
. . . . AustraliaDarwin2_CS_18M_2011_01_13 (
. . . . . . . . GISAID HA EPI319168
. . . . . . . . 16 Polymorphisms (8 Amino and 8 Silent)
. . . . . . . . 41D,
. . . . . . . . syn47L (CTg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . syn82I (ATc) [H5N1 Human (ATa)],
. . . . . . . . syn93C (TGc),
. . . . . . . . 100N [H1N1 Avian
. . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 141Q,
. . . . . . . . syn170N (AAc) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 208K [H1N1 Avian
. . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 219V,
. . . . . . . . 252L,
. . . . . . . . syn307P (CCc) [H5N1 Bangladesh Human 2011],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human 2007-2010 with Fatalities],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
. . . . . . . . . . . . . . . . . . [H5N1 Cambodia Human 2005],
. . . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . 359A,
. . . . . . . . 377K,
. . . . . . . . syn408E (GAa) [H2N3 Avian],
. . . . . . . . . . . . . . . . . . [H5N1 Bangladesh Human 2011],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human 2007-2010 with Fatalities],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
. . . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . . . . . . . . . . . [WSN_1933],
. . . . . . . . . . . . . . . . . . [WSZ_1933],
. . . . . . . . . . . . . . . . . . [1918],
. . . . . . . . syn446K (AAa) [WSZ_1933],
. . . . . . . . syn475D (GAc) [H5N1 Egypt Human 2009 with 196H],
. . . . . . . . . . . . . . . . . . [WSN_1933],
. . . . . . . . . . . . . . . . . . [WSZ_1933],
. . . . . . . . . . . . . . . . . . [1918])
. . . . AustraliaDarwin2_CS_18M_2011_01_13 (
. . . . . . . . GISAID NA EPI319167
. . . . . . . . 10 Polymorphisms (2 Amino and 8 Silent)
. . . . . . . . syn4N (AAt) [H5N1 Avian and Human],
. . . . . . . . syn5Q (CAg)) [H5N1 Avian and Human],
. . . . . . . . syn89S (TCt) [H1N1 Avian],
. . . . . . . . syn126P (CCt) [H6N2 Avian],
. . . . . . . . . . . . . . . . . . [H1N1 Avian (Cat)],
. . . . . . . . syn229S (TCc) [H1N1 Avian],
. . . . . . . . syn236G (GGc) [H1N1 Avian],
. . . . . . . . syn241V (GTg) [H1N1 Avian],
. . . . . . . . 247N,
. . . . . . . . syn268E (GAg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 299A)
. . . . AustraliaDarwin2_18M_2011_01_13 (
. . . . . . . . GISAID HA EPI302351
. . . . . . . . 16 Polymorphisms (8 Amino and 8 Silent)
. . . . . . . . 41D,
. . . . . . . . syn47L (CTg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . syn82I (ATc) [H5N1 Human (ATa)],
. . . . . . . . syn93C (TGc),
. . . . . . . . 100N [H1N1 Avian
. . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 141Q,
. . . . . . . . syn170N (AAc) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 208K [H1N1 Avian
. . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 219V,
. . . . . . . . 252L,
. . . . . . . . syn307P (CCc) [H5N1 Bangladesh Human 2011],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human 2007-2010 with Fatalities],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
. . . . . . . . . . . . . . . . . . [H5N1 Cambodia Human 2005],
. . . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . 359A,
. . . . . . . . 377K,
. . . . . . . . syn408E (GAa) [H2N3 Avian],
. . . . . . . . . . . . . . . . . . [H5N1 Bangladesh Human 2011],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human 2007-2010 with Fatalities],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
. . . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . . . . . . . . . . . [WSN_1933],
. . . . . . . . . . . . . . . . . . [WSZ_1933],
. . . . . . . . . . . . . . . . . . [1918],
. . . . . . . . syn446K (AAa) [WSZ_1933],
. . . . . . . . syn475D (GAc) [H5N1 Egypt Human 2009 with 196H],
. . . . . . . . . . . . . . . . . . [WSN_1933],
. . . . . . . . . . . . . . . . . . [WSZ_1933],
. . . . . . . . . . . . . . . . . . [1918])
. . . . AustraliaDarwin2_18M_2011_01_13 (
. . . . . . . . GISAID NA EPI302350
. . . . . . . . 10 Polymorphisms (2 Amino and 8 Silent)
. . . . . . . . syn4N (AAt) [H5N1 Avian and Human],
. . . . . . . . syn5Q (CAg)) [H5N1 Avian and Human],
. . . . . . . . syn89S (TCt) [H1N1 Avian],
. . . . . . . . syn126P (CCt) [H6N2 Avian],
. . . . . . . . . . . . . . . . . . [H1N1 Avian (Cat)],
. . . . . . . . syn229S (TCc) [H1N1 Avian],
. . . . . . . . syn236G (GGc) [H1N1 Avian],
. . . . . . . . syn241V (GTg) [H1N1 Avian],
. . . . . . . . 247N,
. . . . . . . . syn268E (GAg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 299A)
. . . . Brunei1_2011_01_13 (
. . . . . . . . GISAID HA EPI319180
. . . . . . . . 6 Polymorphisms (3 Amino and 3 Silent)
. . . . . . . . 188T,
. . . . . . . . syn338G (GGc) [H5N1 Human 2011],
. . . . . . . . 377K,
. . . . . . . . syn388K (AAa) [H5N1 Human 2005, 2011],
. . . . . . . . 454N,
. . . . . . . . syn527L (TTa) [H5N1 Human 2005, 2011 (cTa)])
. . . . Brunei1_2011_01_13 (
. . . . . . . . GISAID NA EPI319179
. . . . . . . . 14 Polymorphisms (6 Amino and 8 Silent)
. . . . . . . . syn4N (AAt) [H5N1 Avian and Human],
. . . . . . . . syn5Q (CAg)) [H5N1 Avian and Human],
. . . . . . . . 40I [H1N1 Avian
. . . . . . . . . . . . . . with pH1N1υ polymorphisms],
. . . . . . . . 46T [H1N1 Avian
. . . . . . . . . . . . . . with pH1N1υ polymorphisms],
. . . . . . . . . . . [H1N1 Camel],
. . . . . . . . 95I,
. . . . . . . . syn157T (ACt) [H6N2 Avian],
. . . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . syn229S (TCc) [H1N1 Avian],
. . . . . . . . syn240T (ACc) [H1N1 Avian wt],
. . . . . . . . 241I [H1N1 Avian wt],
. . . . . . . . 247N,
. . . . . . . . syn353Y (TAt) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with pH1N1υ polymorphisms],
. . . . . . . . 369K [H1N1 Avian
. . . . . . . . . . . . . . . . with pH1N1υ polymorphisms],
. . . . . . . . . . . . [H4N6 Avian 2010],
. . . . . . . . . . . . [H12N6 Avian],
. . . . . . . . syn377P (CCa) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with pH1N1υ polymorphisms],
. . . . . . . . syn426L (tTA) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with pH1N1υ polymorphisms])
2011-06-11
2011-06-09
Sweden Signals Rapid Zoonosis from Avian H1N1 on Emergent Tertiary SubClade
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 Updated
2011-06-09
On 2011-06-07, the Swedish Institute for Infectious Disease Control published one pH1N1 sequence at GISAID sampled in February 2011. Six of the HA revisions are commonly found on sequences from the historical Avian H1N1 reservoir with the HA syn221P being conserved in the Avian species across both major circulating human Influenza A serotypes, H1N1 and H3N2. This heavily avian background appears to be transmitting well in humans with cases in Switzerland, France and Estonia that continue the avian influence pattern.
A very practical implication is that many of these Avian sequences bearing the noted individual polymorphisms from this Swedish 208K_219V pH1N1 SubClade 5 sequence also carry polymorphisms that have been demonstrated on another pH1N1 subclade, the HA 189T-bearing Upsilon with a 5.8% Case Fatality Rate. When several of the circulating human subclades are filling with Avian polymorphisms that are multiply co-located on single Avian reservoir sequences, expectations of zoonoses onto pH1N1 are heightened while the currently documented polymorphism-jumping between these very attractant pH1N1 dominant subclades is ensured.
Viable permutations rise.
“Everything that rises must converge.”
. . . . SwedenLinkoping8_20F_2011_02_17 (
. . . . . . . . GISAID HA EPI319566
. . . . . . . . 11 Polymorphisms (5 Amino and 6 Silent)
. . . . . . . . syn47L (CTg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 100N [H1N1 Avian
. . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . syn102E (GAa) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . syn170N (AAc) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 208K [H1N1 Avian
. . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 219V,
. . . . . . . . syn221P (CCt) [H3N2 Avian
. . . . . . . . . . . . . . . . . . . . . . with 157S, 159S, syn287G],
. . . . . . . . . . . . . . . . . . [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 252L,
. . . . . . . . syn319T (ACg),
. . . . . . . . 377K,
. . . . . . . . syn446K (AAa))
. . . . SwedenLinkoping8_20F _2011_02_17 (
. . . . . . . . GISAID NA EPI319567
. . . . . . . . 7 Polymorphisms (3 Amino and 4 Silent)
. . . . . . . . syn60T (ACc),
. . . . . . . . 81A,
. . . . . . . . syn138A (GCt),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa))
Supporting Sequences
. . . . Estonia55306_3F_2011_03_03 (
. . . . . . . . GISAID HA EPI319465
. . . . . . . . 12 Polymorphisms (5 Amino and 7 Silent)
. . . . . . . . syn47L (CTg),
. . . . . . . . 100N,
. . . . . . . . syn102E (GAa),
. . . . . . . . syn170N (AAc),
. . . . . . . . 208K,
. . . . . . . . 219V,
. . . . . . . . syn221P (CCt),
. . . . . . . . 252L,
. . . . . . . . syn254P (CCa) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . syn319T (ACg),
. . . . . . . . 377K,
. . . . . . . . syn446K (AAa))
. . . . Estonia55306_3F_2011_03_03 (
. . . . . . . . GISAID NA EPI319466
. . . . . . . . 6 Polymorphisms (2 Amino and 4 Silent)
. . . . . . . . syn119E (GAg),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc))
. . . . Estonia54375_51F_2011_02_11 (
. . . . . . . . GISAID HA EPI319459
. . . . . . . . 11 Polymorphisms (5 Amino and 6 Silent)
. . . . . . . . syn47L (CTg),
. . . . . . . . 100N,
. . . . . . . . syn102E (GAa),
. . . . . . . . syn170N (AAc),
. . . . . . . . 208K,
. . . . . . . . 219V,
. . . . . . . . syn221P (CCt),
. . . . . . . . 252L,
. . . . . . . . syn319T (ACg),
. . . . . . . . 377K,
. . . . . . . . syn446K (AAa))
. . . . Estonia54375_51F_2011_02_11 (
. . . . . . . . GISAID NA EPI319460
. . . . . . . . 9 Polymorphisms (3 Amino and 6 Silent)
. . . . . . . . syn60T (ACc),
. . . . . . . . syn67V (GTc),
. . . . . . . . 81A,
. . . . . . . . syn138A (GCt),
. . . . . . . . syn221N (AAt),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa))
. . . . Estonia54132_18F_2011_02_08 (
. . . . . . . . GISAID HA EPI319457
. . . . . . . . 11 Polymorphisms (5 Amino and 6 Silent)
. . . . . . . . syn47L (CTg),
. . . . . . . . 100N,
. . . . . . . . syn102E (GAa),
. . . . . . . . syn170N (AAc),
. . . . . . . . 208K,
. . . . . . . . 219V,
. . . . . . . . syn221P (CCt),
. . . . . . . . 252L,
. . . . . . . . syn319T (ACg),
. . . . . . . . 377K,
. . . . . . . . syn446K (AAa))
. . . . Estonia54132_18F_2011_02_08 (
. . . . . . . . GISAID NA EPI319458
. . . . . . . . 8 Polymorphisms (3 Amino and 5 Silent)
. . . . . . . . syn24L (TTg),
. . . . . . . . 81A,
. . . . . . . . syn138A (GCt),
. . . . . . . . syn216I (ATt),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa))
. . . . SwitzerlandGeneva4201955_xF_2011_01_06 (
. . . . . . . . GISAID HA EPI309651
. . . . . . . . 11 Polymorphisms (5 Amino and 6 Silent)
. . . . . . . . syn47L (CTg),
. . . . . . . . 100N,
. . . . . . . . syn102E (GAa),
. . . . . . . . 157N mix wt,
. . . . . . . . syn170N (AAc),
. . . . . . . . 208K,
. . . . . . . . 219V,
. . . . . . . . syn221P (CCt),
. . . . . . . . 252L,
. . . . . . . . 377K,
. . . . . . . . syn446K (AAa))
. . . . SwitzerlandGeneva4201955_xF_2011_01_06 (
. . . . . . . . GISAID NA EPI309652
. . . . . . . . 9 Polymorphisms (3 Amino and 6 Silent)
. . . . . . . . 81A,
. . . . . . . . syn138A (GCt),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . syn271A (GCt),
. . . . . . . . syn298G (GGa),
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn449N (AAt))
. . . . FranceLyon3_58x_2010_12_31 (
. . . . . . . . GISAID HA EPI319497
. . . . . . . . 11 Polymorphisms (5 Amino and 6 Silent)
. . . . . . . . syn47L (CTg),
. . . . . . . . 100N,
. . . . . . . . syn102E (GAa),
. . . . . . . . syn170N (AAc),
. . . . . . . . 208K,
. . . . . . . . 219V,
. . . . . . . . syn221P (CCt),
. . . . . . . . 252L,
. . . . . . . . syn319T (ACg),
. . . . . . . . 377K,
. . . . . . . . syn446K (AAa))
. . . . FranceLyon3_58x_2010_12_31 (
. . . . . . . . GISAID NA EPI319498
. . . . . . . . 9 Polymorphisms (3 Amino and 6 Silent)
. . . . . . . . syn60T (ACc),
. . . . . . . . 81A,
. . . . . . . . syn124C (TGt),
. . . . . . . . syn138A (GCt),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn382G (GGa))
. . . . Iowa04_2009_04_24 (
. . . . . . . . GISAID HA EPI179262
. . . . . . . . 3 Polymorphisms (1 Amino and 2 Silent)
. . . . . . . . 206S,
. . . . . . . . syn221P (CCt),
. . . . . . . . syn498L (TTg))
. . . . Iowa04_2009_04_24 (
. . . . . . . . GISAID NA EPI186289
. . . . . . . . 2 Polymorphisms (0 Amino and 2 Silent)
. . . . . . . . syn306F (TTt),
. . . . . . . . syn307N (AAt))
Last Updated
2011-06-09
On 2011-06-07, the Swedish Institute for Infectious Disease Control published one pH1N1 sequence at GISAID sampled in February 2011. Six of the HA revisions are commonly found on sequences from the historical Avian H1N1 reservoir with the HA syn221P being conserved in the Avian species across both major circulating human Influenza A serotypes, H1N1 and H3N2. This heavily avian background appears to be transmitting well in humans with cases in Switzerland, France and Estonia that continue the avian influence pattern.
A very practical implication is that many of these Avian sequences bearing the noted individual polymorphisms from this Swedish 208K_219V pH1N1 SubClade 5 sequence also carry polymorphisms that have been demonstrated on another pH1N1 subclade, the HA 189T-bearing Upsilon with a 5.8% Case Fatality Rate. When several of the circulating human subclades are filling with Avian polymorphisms that are multiply co-located on single Avian reservoir sequences, expectations of zoonoses onto pH1N1 are heightened while the currently documented polymorphism-jumping between these very attractant pH1N1 dominant subclades is ensured.
Viable permutations rise.
“Everything that rises must converge.”
. . . . SwedenLinkoping8_20F_2011_02_17 (
. . . . . . . . GISAID HA EPI319566
. . . . . . . . 11 Polymorphisms (5 Amino and 6 Silent)
. . . . . . . . syn47L (CTg) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 100N [H1N1 Avian
. . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . syn102E (GAa) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . syn170N (AAc) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 208K [H1N1 Avian
. . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 219V,
. . . . . . . . syn221P (CCt) [H3N2 Avian
. . . . . . . . . . . . . . . . . . . . . . with 157S, 159S, syn287G],
. . . . . . . . . . . . . . . . . . [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 252L,
. . . . . . . . syn319T (ACg),
. . . . . . . . 377K,
. . . . . . . . syn446K (AAa))
. . . . SwedenLinkoping8_20F _2011_02_17 (
. . . . . . . . GISAID NA EPI319567
. . . . . . . . 7 Polymorphisms (3 Amino and 4 Silent)
. . . . . . . . syn60T (ACc),
. . . . . . . . 81A,
. . . . . . . . syn138A (GCt),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa))
Supporting Sequences
. . . . Estonia55306_3F_2011_03_03 (
. . . . . . . . GISAID HA EPI319465
. . . . . . . . 12 Polymorphisms (5 Amino and 7 Silent)
. . . . . . . . syn47L (CTg),
. . . . . . . . 100N,
. . . . . . . . syn102E (GAa),
. . . . . . . . syn170N (AAc),
. . . . . . . . 208K,
. . . . . . . . 219V,
. . . . . . . . syn221P (CCt),
. . . . . . . . 252L,
. . . . . . . . syn254P (CCa) [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . syn319T (ACg),
. . . . . . . . 377K,
. . . . . . . . syn446K (AAa))
. . . . Estonia55306_3F_2011_03_03 (
. . . . . . . . GISAID NA EPI319466
. . . . . . . . 6 Polymorphisms (2 Amino and 4 Silent)
. . . . . . . . syn119E (GAg),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc))
. . . . Estonia54375_51F_2011_02_11 (
. . . . . . . . GISAID HA EPI319459
. . . . . . . . 11 Polymorphisms (5 Amino and 6 Silent)
. . . . . . . . syn47L (CTg),
. . . . . . . . 100N,
. . . . . . . . syn102E (GAa),
. . . . . . . . syn170N (AAc),
. . . . . . . . 208K,
. . . . . . . . 219V,
. . . . . . . . syn221P (CCt),
. . . . . . . . 252L,
. . . . . . . . syn319T (ACg),
. . . . . . . . 377K,
. . . . . . . . syn446K (AAa))
. . . . Estonia54375_51F_2011_02_11 (
. . . . . . . . GISAID NA EPI319460
. . . . . . . . 9 Polymorphisms (3 Amino and 6 Silent)
. . . . . . . . syn60T (ACc),
. . . . . . . . syn67V (GTc),
. . . . . . . . 81A,
. . . . . . . . syn138A (GCt),
. . . . . . . . syn221N (AAt),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa))
. . . . Estonia54132_18F_2011_02_08 (
. . . . . . . . GISAID HA EPI319457
. . . . . . . . 11 Polymorphisms (5 Amino and 6 Silent)
. . . . . . . . syn47L (CTg),
. . . . . . . . 100N,
. . . . . . . . syn102E (GAa),
. . . . . . . . syn170N (AAc),
. . . . . . . . 208K,
. . . . . . . . 219V,
. . . . . . . . syn221P (CCt),
. . . . . . . . 252L,
. . . . . . . . syn319T (ACg),
. . . . . . . . 377K,
. . . . . . . . syn446K (AAa))
. . . . Estonia54132_18F_2011_02_08 (
. . . . . . . . GISAID NA EPI319458
. . . . . . . . 8 Polymorphisms (3 Amino and 5 Silent)
. . . . . . . . syn24L (TTg),
. . . . . . . . 81A,
. . . . . . . . syn138A (GCt),
. . . . . . . . syn216I (ATt),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa))
. . . . SwitzerlandGeneva4201955_xF_2011_01_06 (
. . . . . . . . GISAID HA EPI309651
. . . . . . . . 11 Polymorphisms (5 Amino and 6 Silent)
. . . . . . . . syn47L (CTg),
. . . . . . . . 100N,
. . . . . . . . syn102E (GAa),
. . . . . . . . 157N mix wt,
. . . . . . . . syn170N (AAc),
. . . . . . . . 208K,
. . . . . . . . 219V,
. . . . . . . . syn221P (CCt),
. . . . . . . . 252L,
. . . . . . . . 377K,
. . . . . . . . syn446K (AAa))
. . . . SwitzerlandGeneva4201955_xF_2011_01_06 (
. . . . . . . . GISAID NA EPI309652
. . . . . . . . 9 Polymorphisms (3 Amino and 6 Silent)
. . . . . . . . 81A,
. . . . . . . . syn138A (GCt),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . syn271A (GCt),
. . . . . . . . syn298G (GGa),
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn449N (AAt))
. . . . FranceLyon3_58x_2010_12_31 (
. . . . . . . . GISAID HA EPI319497
. . . . . . . . 11 Polymorphisms (5 Amino and 6 Silent)
. . . . . . . . syn47L (CTg),
. . . . . . . . 100N,
. . . . . . . . syn102E (GAa),
. . . . . . . . syn170N (AAc),
. . . . . . . . 208K,
. . . . . . . . 219V,
. . . . . . . . syn221P (CCt),
. . . . . . . . 252L,
. . . . . . . . syn319T (ACg),
. . . . . . . . 377K,
. . . . . . . . syn446K (AAa))
. . . . FranceLyon3_58x_2010_12_31 (
. . . . . . . . GISAID NA EPI319498
. . . . . . . . 9 Polymorphisms (3 Amino and 6 Silent)
. . . . . . . . syn60T (ACc),
. . . . . . . . 81A,
. . . . . . . . syn124C (TGt),
. . . . . . . . syn138A (GCt),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn382G (GGa))
. . . . Iowa04_2009_04_24 (
. . . . . . . . GISAID HA EPI179262
. . . . . . . . 3 Polymorphisms (1 Amino and 2 Silent)
. . . . . . . . 206S,
. . . . . . . . syn221P (CCt),
. . . . . . . . syn498L (TTg))
. . . . Iowa04_2009_04_24 (
. . . . . . . . GISAID NA EPI186289
. . . . . . . . 2 Polymorphisms (0 Amino and 2 Silent)
. . . . . . . . syn306F (TTt),
. . . . . . . . syn307N (AAt))
2011-06-07
HA 189T Upsilon in Czech Republic Recombines with 188T Tau SubClade
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 Updated
2011-06-09
On 2011-06-06, the National Institute of Medical Research of the UK published 56 pH1N1 sequences at GISAID sampled in a time period spanning late 2010 to early 2011 with the geographic majority from Europe. A subclade bearing HA 189T that is 230I-permissive gains 3 members with this deposit, but more importantly the level of polymorphic subclade jumping has accelerated as previously discussed. The 3' end of a well-defined 188T-bearing subclade from fatal and severe cases in the UK has recombined onto the rare Upsilon subclade (53 sequences, 5.8% CFR).
The 3 additions to pH1N1υ are detailed, with the recombinant CzechRepublic32_xM_2011_01_18 shown first. Though 189T has been found upon 188T backgrounds in several pandemic geographies, this 189T Czech sequence marks the first fully defined, contiguous range, triple polymorphism recombination of 188T background markers onto the 189T Upsilon subclade.
Trailing the polymorphism lists of the 3 Upsilon additions, we also detail two of the several instances of the single polymorphism HA 189T arriving on a 188T background.
A deposit made 2011-06-05 at GenBank from Fondazione IRCCS Policlinico San Matteo in Pavia, Italy demonstrates another particular instance of subclade elasticity. A similar crossing of the Czech pH1N1 Tau and Upsilon subclades is found in reverse on a Palermo HA segment sampled via a deep lung wash from a patient suffering Acute Respiratory Distress Syndrome (ARDS). This 188T Tau subclade sequence, ItalyPalermo02_2011_01_31_severe, takes an 189T from Upsilon and then adds a 208K from an emerging tertiary subclade, resulting in a single 225G-bearing Italian HA segment holding data from three dominant subclades.
These developments suggest the merit of sampling and directly sequencing a wider variety of sources and tissue types. The investigators from Pavia have now established a working benchmark for accurately surfacing the actual causative strain sequences from severely ill patients.
On 2011-05-19, the Cantacuzino Institute of Bucharest, Romania deposited 52 sequences at GenBank, representing partial segments (several with potential 3' end recombination from non-pH1N1 primer-matching strains). A similar adoption of HA 189T onto a known circulating 188T background occurred on RomaniaBihor51551_54F_2011_01_31 with the unusual HA 296R unique to this Romanian deposit and a single 2009 Malaysian HA. Recall that the polymorphism HA 296H was correlated to numerous fatalities during the early pandemic in Brasil.
Co-location of these transferable components within zoonotic reservoirs provides ample opportunity for exchange. Expectations should be reset for future pH1N1 antigenic variation as these three dominant subclades continue to demonstrate active cooperation in developing viable Vaccine Escape polymorphisms and then sharing them when perfected.
Upsilon
. . . . CzechRepublic32_xM_2011_01_18 (
. . . . . . . . GISAID HA EPI319447
. . . . . . . . 13 Polymorphisms (6 Amino and 7 Silent)
. . . . . . . . 34D,
. . . . . . . . syn87S (AGc),
. . . . . . . . syn118E (GAa),
. . . . . . . . 165N,
. . . . . . . . 189T,
. . . . . . . . syn213F (TTt),
. . . . . . . . 218T [Texas03_M1C2_38M_2010_06_01],
. . . . . . . . . . . . . [H5N1 Egypt Human 2009],
. . . . . . . . syn287G (GGg),
. . . . . . . . syn305K (AAg),
. . . . . . . . syn346G (GGa),
. . . . . . . . 377K,
. . . . . . . . syn448L (TTg),
. . . . . . . . 454N)
. . . . AlgeriaG388_1F_2010_12_21 (
. . . . . . . . GISAID HA EPI319430
. . . . . . . . 11 Polymorphisms (4 Amino and 7 Silent)
. . . . . . . . 34D,
. . . . . . . . syn118E (GAa),
. . . . . . . . syn158G (GGg),
. . . . . . . . 165N,
. . . . . . . . 189T,
. . . . . . . . syn213F (TTt),
. . . . . . . . 275I,
. . . . . . . . syn287G (GGg),
. . . . . . . . syn305K (AAg),
. . . . . . . . syn346G (GGa),
. . . . . . . . syn397G (GGc))
. . . . Estonia55236_30M_2011_03_02 (
. . . . . . . . GISAID HA EPI319464
. . . . . . . . 13 Polymorphisms (5 Amino and 8 Silent)
. . . . . . . . 34D,
. . . . . . . . 42W,
. . . . . . . . syn87S (AGc),
. . . . . . . . syn118E (GAa),
. . . . . . . . 165N,
. . . . . . . . 189T,
. . . . . . . . syn213F (TTt),
. . . . . . . . 275I,
. . . . . . . . syn287G (GGg),
. . . . . . . . syn305K (AAg),
. . . . . . . . syn346G (GGa),
. . . . . . . . syn397G (GGc),
. . . . . . . . syn469E (GAg))
Italy
. . . . ItalyPalermo02_2011_01_31_severe (
. . . . . . . . GenBank HA JN017179
. . . . . . . . BronchoAlveolar Lavage
. . . . . . . . 12 Polymorphisms (7 Amino and 5 Silent)
. . . . . . . . 100N,
. . . . . . . . syn116R (AGa),
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . 189T,
. . . . . . . . 208K,
. . . . . . . . 225G,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . syn428L (tTG),
. . . . . . . . syn448L (TTg),
. . . . . . . . 454N)
Romania
. . . . RomaniaBihor51551_54F_2011_01_31 (
. . . . . . . . GenBank HA CY090796
. . . . . . . . 6 Polymorphisms (4 Amino and 2 Silent)
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . 189T,
. . . . . . . . syn215P (CCa),
. . . . . . . . 296R [GISAID Rare 11 – Romania (10) & 2009 Malaysia],
. . . . . . . . HA Truncated after aa296)
Last Updated
2011-06-09
On 2011-06-06, the National Institute of Medical Research of the UK published 56 pH1N1 sequences at GISAID sampled in a time period spanning late 2010 to early 2011 with the geographic majority from Europe. A subclade bearing HA 189T that is 230I-permissive gains 3 members with this deposit, but more importantly the level of polymorphic subclade jumping has accelerated as previously discussed. The 3' end of a well-defined 188T-bearing subclade from fatal and severe cases in the UK has recombined onto the rare Upsilon subclade (53 sequences, 5.8% CFR).
The 3 additions to pH1N1υ are detailed, with the recombinant CzechRepublic32_xM_2011_01_18 shown first. Though 189T has been found upon 188T backgrounds in several pandemic geographies, this 189T Czech sequence marks the first fully defined, contiguous range, triple polymorphism recombination of 188T background markers onto the 189T Upsilon subclade.
Trailing the polymorphism lists of the 3 Upsilon additions, we also detail two of the several instances of the single polymorphism HA 189T arriving on a 188T background.
A deposit made 2011-06-05 at GenBank from Fondazione IRCCS Policlinico San Matteo in Pavia, Italy demonstrates another particular instance of subclade elasticity. A similar crossing of the Czech pH1N1 Tau and Upsilon subclades is found in reverse on a Palermo HA segment sampled via a deep lung wash from a patient suffering Acute Respiratory Distress Syndrome (ARDS). This 188T Tau subclade sequence, ItalyPalermo02_2011_01_31_severe, takes an 189T from Upsilon and then adds a 208K from an emerging tertiary subclade, resulting in a single 225G-bearing Italian HA segment holding data from three dominant subclades.
These developments suggest the merit of sampling and directly sequencing a wider variety of sources and tissue types. The investigators from Pavia have now established a working benchmark for accurately surfacing the actual causative strain sequences from severely ill patients.
On 2011-05-19, the Cantacuzino Institute of Bucharest, Romania deposited 52 sequences at GenBank, representing partial segments (several with potential 3' end recombination from non-pH1N1 primer-matching strains). A similar adoption of HA 189T onto a known circulating 188T background occurred on RomaniaBihor51551_54F_2011_01_31 with the unusual HA 296R unique to this Romanian deposit and a single 2009 Malaysian HA. Recall that the polymorphism HA 296H was correlated to numerous fatalities during the early pandemic in Brasil.
Co-location of these transferable components within zoonotic reservoirs provides ample opportunity for exchange. Expectations should be reset for future pH1N1 antigenic variation as these three dominant subclades continue to demonstrate active cooperation in developing viable Vaccine Escape polymorphisms and then sharing them when perfected.
Upsilon
. . . . CzechRepublic32_xM_2011_01_18 (
. . . . . . . . GISAID HA EPI319447
. . . . . . . . 13 Polymorphisms (6 Amino and 7 Silent)
. . . . . . . . 34D,
. . . . . . . . syn87S (AGc),
. . . . . . . . syn118E (GAa),
. . . . . . . . 165N,
. . . . . . . . 189T,
. . . . . . . . syn213F (TTt),
. . . . . . . . 218T [Texas03_M1C2_38M_2010_06_01],
. . . . . . . . . . . . . [H5N1 Egypt Human 2009],
. . . . . . . . syn287G (GGg),
. . . . . . . . syn305K (AAg),
. . . . . . . . syn346G (GGa),
. . . . . . . . 377K,
. . . . . . . . syn448L (TTg),
. . . . . . . . 454N)
. . . . AlgeriaG388_1F_2010_12_21 (
. . . . . . . . GISAID HA EPI319430
. . . . . . . . 11 Polymorphisms (4 Amino and 7 Silent)
. . . . . . . . 34D,
. . . . . . . . syn118E (GAa),
. . . . . . . . syn158G (GGg),
. . . . . . . . 165N,
. . . . . . . . 189T,
. . . . . . . . syn213F (TTt),
. . . . . . . . 275I,
. . . . . . . . syn287G (GGg),
. . . . . . . . syn305K (AAg),
. . . . . . . . syn346G (GGa),
. . . . . . . . syn397G (GGc))
. . . . Estonia55236_30M_2011_03_02 (
. . . . . . . . GISAID HA EPI319464
. . . . . . . . 13 Polymorphisms (5 Amino and 8 Silent)
. . . . . . . . 34D,
. . . . . . . . 42W,
. . . . . . . . syn87S (AGc),
. . . . . . . . syn118E (GAa),
. . . . . . . . 165N,
. . . . . . . . 189T,
. . . . . . . . syn213F (TTt),
. . . . . . . . 275I,
. . . . . . . . syn287G (GGg),
. . . . . . . . syn305K (AAg),
. . . . . . . . syn346G (GGa),
. . . . . . . . syn397G (GGc),
. . . . . . . . syn469E (GAg))
Italy
. . . . ItalyPalermo02_2011_01_31_severe (
. . . . . . . . GenBank HA JN017179
. . . . . . . . BronchoAlveolar Lavage
. . . . . . . . 12 Polymorphisms (7 Amino and 5 Silent)
. . . . . . . . 100N,
. . . . . . . . syn116R (AGa),
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . 189T,
. . . . . . . . 208K,
. . . . . . . . 225G,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . syn428L (tTG),
. . . . . . . . syn448L (TTg),
. . . . . . . . 454N)
Romania
. . . . RomaniaBihor51551_54F_2011_01_31 (
. . . . . . . . GenBank HA CY090796
. . . . . . . . 6 Polymorphisms (4 Amino and 2 Silent)
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . 189T,
. . . . . . . . syn215P (CCa),
. . . . . . . . 296R [GISAID Rare 11 – Romania (10) & 2009 Malaysia],
. . . . . . . . HA Truncated after aa296)
2011-06-03
Sweden Demonstrates Extensive Winter 2011 Diversity with 5 pH1N1 SubClades Represented on 11 Deposited Sequences
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 Updated
2011-06-03
Across 2011-05-30 and 05-31, the Swedish Institute for Infectious Disease Control published 11 pH1N1 sequences at GISAID sampled in a time period spanning January to April 2011 with the majority in February (6). The two deposits merit discussion due to the wide variety of backgrounds demonstrated across such a small population of sequences.
A minimum of 5 Pandemic H1N1 subclades are represented in these 11 Swedish sequences. More than one represented subclade carries revisions that have been associated with laboratory-determined “Low Reactor” status or with illness in previously vaccinated subjects. None of the 11 Swedish sequences fall onto the Pandemic H1N1 Upsilon subclade (pH1N1υ), but several, including one Swedish fatality of a 10 year old male, have crossover polymorphisms previously described in the pH1N1υ superset.
130 polymorphisms (67 amino and 63 silent) are found on these 11 HA segments with 69 distinct HA changes. The 11 NA segments demonstrate 77 polymorphisms (41 amino and 36 silent) with 38 distinct NA changes. 207 total polymorphisms on 11 Swedish sequences (HA + NA) averages to 18.8 changes per sequence. A minimum of 5 subclades with 18 changes per sequence, many at known epitopes (antigenic sites), factors as a significantly difficult target to match with a “single-strain per serotype” vaccine strategy.
Measurable potential for Vaccine Escape increases with circulating diversity as found on these moving targets in Scandinavia and with the clinical and experimental indications of vaccine failure, e.g. HA 128D, HA 158E, et al.
Four of the 11 HA sequences demonstrate 188T of the first pH1N1 emergent nucleotide coding and 2 of those Swedish 188T sequences additionally carry HA 158E in a mixture with wild type. Another 4 of the 11 HA sequences demonstrate 186P with one additionally carrying HA 158E in a mixture with wild type on a background with avian influenza polymorphisms. A concentration of 3 HA 158E revisions in 11 samples mimics the high levels found previously in other Asian and European geographies. The penetration of HA revisions between aa156 and aa159 in Scandinavia is crossing backgrounds and appears to be accelerating.
The fatal case, SwedenMalmoe5_10M_2011_04_21_f, carries 12 HA changes including revision at aa144 (positional to pH1N1υ 144E & 144T) and equality to the pH1N1υ superset at syn287G & 377K. Eight NA changes on the fatal sequence bring the polymorphic total to 20. That total suggests that aggressive viral revision is correlated to fatal and severe cases. These recent high incidences of polymorphism jumping between human subclades appear to follow the dictates of co-location on zoonotic avian sequences.
HA
. . . . SwedenMalmoe5_10M_2011_04_21_f (
. . . . . . . . GISAID EPI318269
. . . . . . . . 12 Polymorphisms (6 Amino and 6 Silent)
. . . . . . . . 137T,
. . . . . . . . 144S,
. . . . . . . . syn163K (AAa),
. . . . . . . . 186P,
. . . . . . . . syn251L (CTg),
. . . . . . . . syn287G (GGg),
. . . . . . . . syn293L (CTt),
. . . . . . . . 298V,
. . . . . . . . syn363G (GGg),
. . . . . . . . 377K,
. . . . . . . . syn474C (TGt),
. . . . . . . . 482I)
. . . . SwedenUppsala6_67F_2011_03_11 (
. . . . . . . . GISAID EPI318263
. . . . . . . . 13 Polymorphisms (6 Amino and 7 Silent)
. . . . . . . . 137T,
. . . . . . . . 144S,
. . . . . . . . syn163K (AAa),
. . . . . . . . 186P,
. . . . . . . . syn251L (CTg),
. . . . . . . . syn287G (GGg),
. . . . . . . . syn293L (CTt),
. . . . . . . . 298V,
. . . . . . . . syn363G (GGg),
. . . . . . . . 377K,
. . . . . . . . syn474C (TGt),
. . . . . . . . syn480E (GAg),
. . . . . . . . 482I)
. . . . SwedenLinkoping7_19F_2011_03_09 (
. . . . . . . . GISAID EPI318260
. . . . . . . . 15 Polymorphisms (7 Amino and 8 Silent)
. . . . . . . . syn42G (GGa),
. . . . . . . . syn47L (CTg),
. . . . . . . . syn58C (TGc),
. . . . . . . . syn82I (ATc),
. . . . . . . . syn93C (TGc),
. . . . . . . . 100N,
. . . . . . . . 141Q,
. . . . . . . . syn170N (AAc),
. . . . . . . . 208K,
. . . . . . . . 219V,
. . . . . . . . 252L,
. . . . . . . . syn307P (CCc),
. . . . . . . . 359A,
. . . . . . . . 377K,
. . . . . . . . syn446K (AAa))
. . . . SwedenStockholm14_32M_2011_02_15 (
. . . . . . . . GISAID EPI318257
. . . . . . . . 18 Polymorphisms (9 Amino and 9 Silent)
. . . . . . . . syn10Y (TAc),
. . . . . . . . syn33V (GTc),
. . . . . . . . syn34N (AAt),
. . . . . . . . syn99I (ATt),
. . . . . . . . 132S,
. . . . . . . . syn139C (TGc),
. . . . . . . . 145R,
. . . . . . . . 146G,
. . . . . . . . 158E mix wt,
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . 454N,
. . . . . . . . syn456L (TTg),
. . . . . . . . syn465N (AAt),
. . . . . . . . 496S,
. . . . . . . . syn538F (TTt))
. . . . SwedenStockholm12_2011_02_13 (
. . . . . . . . GISAID EPI318241
. . . . . . . . 7 Polymorphisms (4 Amino and 3 Silent)
. . . . . . . . 100N,
. . . . . . . . 188T,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . syn431L (tTA),
. . . . . . . . 454N,
. . . . . . . . syn537S (AGc))
. . . . SwedenStockholm13_2011_02_09_sH1N1 (
. . . . . . . . GISAID EPI318247
. . . . . . . . 12 Polymorphisms (5 Amino and 7 Silent)
. . . . . . . . syn41N (AAt),
. . . . . . . . 50I,
. . . . . . . . syn154L (tTA) [swThailandCU_CHK4_2009_01
. . . . . . . . . . . . . . . . . . . . . . . . . with syn69E, 100N, syn154L (CTg),
. . . . . . . . . . . . . . . . . . . . . . . . . 189T, syn215P, 298V,
. . . . . . . . . . . . . . . . . . . . . . . . . syn338G, syn346G, syn388K,
. . . . . . . . . . . . . . . . . . . . . . . . . syn448L (cTA), syn474C, 482I],
. . . . . . . . 158E mix wt,
. . . . . . . . 188T,
. . . . . . . . 259T,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . syn388K (AAa),
. . . . . . . . 415E mix wt,
. . . . . . . . 454N,
. . . . . . . . syn527L (TTa))
. . . . SwedenStockholm10_2011_02_06 (
. . . . . . . . GISAID EPI318238
. . . . . . . . 11 Polymorphisms (7 Amino and 4 Silent)
. . . . . . . . 59S,
. . . . . . . . syn69E (GAa) [swThailandCU_CHK4_2009_01
. . . . . . . . . . . . . . . . . . . . . . . . . with syn69E, 100N, syn154L (CTg),
. . . . . . . . . . . . . . . . . . . . . . . . . 189T, syn215P, 298V,
. . . . . . . . . . . . . . . . . . . . . . . . . syn338G, syn346G, syn388K,
. . . . . . . . . . . . . . . . . . . . . . . . . syn448L (cTA), syn474C, 482I],
. . . . . . . . 100N,
. . . . . . . . 166I [Novel to pH1N1 188T SubClades],
. . . . . . . . 188T,
. . . . . . . . syn215P (CCa) [Vladivistok7_2010_12_03 with 188T],
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . 414I [swThailandCU_RA75_2010_01 with 188T],
. . . . . . . . 454N,
. . . . . . . . syn537S (AGc))
. . . . SwedenStockholm11_2011_02_05 (
. . . . . . . . GISAID EPI318235
. . . . . . . . 7 Polymorphisms (4 Amino and 3 Silent)
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . syn448L (TTg) [swThailandCU_CHK4_2009_01
. . . . . . . . . . . . . . . . . . . . . . . . . with syn69E, 100N, syn154L (CTg),
. . . . . . . . . . . . . . . . . . . . . . . . . 189T, syn215P, 298V,
. . . . . . . . . . . . . . . . . . . . . . . . . syn338G, syn346G, syn388K,
. . . . . . . . . . . . . . . . . . . . . . . . . syn448L (cTA), syn474C, 482I],
. . . . . . . . 454N)
. . . . SwedenMalmoe4_2011_02_13 (
. . . . . . . . GISAID EPI318254
. . . . . . . . 7 Polymorphisms (3 Amino and 4 Silent)
. . . . . . . . syn60I (ATc),
. . . . . . . . 128D,
. . . . . . . . syn218A (GCg),
. . . . . . . . syn273T (ACg),
. . . . . . . . 286E,
. . . . . . . . 377K,
. . . . . . . . syn469E (GAg))
. . . . SwedenUmea1_35x_2011_01_28 (
. . . . . . . . GISAID EPI318266
. . . . . . . . 14 Polymorphisms (7 Amino and 7 Silent)
. . . . . . . . syn98F (TTt),
. . . . . . . . 137T,
. . . . . . . . 144S,
. . . . . . . . syn163K (AAa),
. . . . . . . . 186P,
. . . . . . . . syn251L (CTg),
. . . . . . . . syn287G (GGg),
. . . . . . . . syn293L (CTt),
. . . . . . . . 298V,
. . . . . . . . syn363G (GGg),
. . . . . . . . 377K,
. . . . . . . . 397D mix wt,
. . . . . . . . syn474C (TGt),
. . . . . . . . 482I)
. . . . SwedenGothenburg1_2011_01_16 (
. . . . . . . . GISAID EPI318244
. . . . . . . . 14 Polymorphisms (6 Amino and 8 Silent)
. . . . . . . . 137T,
. . . . . . . . 144S,
. . . . . . . . 158E mix wt,
. . . . . . . . syn163K (AAa),
. . . . . . . . 186P,
. . . . . . . . syn251L (CTg),
. . . . . . . . syn287G (GGg),
. . . . . . . . syn293L (CTt),
. . . . . . . . 298V [swThailandCU_CHK4_2009_01
. . . . . . . . . . . . . . . . . . . . . . . . . with syn69E, 100N, syn154L (CTg),
. . . . . . . . . . . . . . . . . . . . . . . . . 189T, syn215P, 298V,
. . . . . . . . . . . . . . . . . . . . . . . . . syn338G, syn346G, syn388K,
. . . . . . . . . . . . . . . . . . . . . . . . . syn448L (cTA), syn474C, 482I],
. . . . . . . . syn346G (GGa),
. . . . . . . . syn363G (GGg),
. . . . . . . . 377K,
. . . . . . . . syn474C (TGt),
. . . . . . . . 482I)
NA
. . . . SwedenMalmoe5_10M_2011_04_21_f (
. . . . . . . . GISAID EPI318270
. . . . . . . . 8 Polymorphisms (4 Amino and 4 Silent)
. . . . . . . . 46T,
. . . . . . . . syn187G (GGt),
. . . . . . . . 313R,
. . . . . . . . syn336G (GGc),
. . . . . . . . syn370G (GGc),
. . . . . . . . 394I,
. . . . . . . . syn430R (CGg),
. . . . . . . . 467V)
. . . . SwedenUppsala6_67F_2011_03_11 (
. . . . . . . . GISAID EPI318264
. . . . . . . . 7 Polymorphisms (4 Amino and 3 Silent)
. . . . . . . . 46T,
. . . . . . . . syn47E (GAg),
. . . . . . . . syn187G (GGt),
. . . . . . . . 313R,
. . . . . . . . 394I,
. . . . . . . . syn430R (CGg),
. . . . . . . . 467V)
. . . . SwedenLinkoping7_19F_2011_03_09 (
. . . . . . . . GISAID EPI318261
. . . . . . . . 6 Polymorphisms (1 Amino and 5 Silent)
. . . . . . . . syn89S (TCt),
. . . . . . . . syn126P (CCt),
. . . . . . . . syn229S (TCc),
. . . . . . . . syn236G (GGc),
. . . . . . . . syn241V (GTg),
. . . . . . . . 299A)
. . . . SwedenStockholm14_32M_2011_02_15 (
. . . . . . . . GISAID EPI318258
. . . . . . . . 8 Polymorphisms (5 Amino and 3 Silent)
. . . . . . . . 20T,
. . . . . . . . 44S,
. . . . . . . . 119K mix wt,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn378N (AAt))
. . . . SwedenMalmoe4_2011_02_13 (
. . . . . . . . GISAID EPI318255
. . . . . . . . 6 Polymorphisms (4 Amino and 2 Silent)
. . . . . . . . 240I,
. . . . . . . . 264I,
. . . . . . . . syn339S (TCa),
. . . . . . . . syn383T (ACt),
. . . . . . . . 397K,
. . . . . . . . 442I)
. . . . SwedenStockholm12_21F_2011_02_13 (
. . . . . . . . GISAID EPI318242
. . . . . . . . 7 Polymorphisms (4 Amino and 3 Silent)
. . . . . . . . 83M,
. . . . . . . . 173K,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc))
. . . . SwedenStockholm13_2011_02_09 (
. . . . . . . . GISAID EPI318248
. . . . . . . . 9 Polymorphisms (5 Amino and 4 Silent)
. . . . . . . . 20T,
. . . . . . . . 40I,
. . . . . . . . 46T,
. . . . . . . . syn157T (ACt),
. . . . . . . . syn229S (TCc),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa))
. . . . SwedenStockholm10_31F_2011_02_06 (
. . . . . . . . GISAID EPI318239
. . . . . . . . 5 Polymorphisms (2 Amino and 3 Silent)
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc))
. . . . SwedenStockholm11_38F_2011_02_05 (
. . . . . . . . GISAID EPI318236
. . . . . . . . 7 Polymorphisms (2 Amino and 5 Silent)
. . . . . . . . syn162P (CCc),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn398E (GAa),
. . . . . . . . syn416D (GAc))
. . . . SwedenUmea1_35x_2011_01_28 (
. . . . . . . . GISAID EPI318267
. . . . . . . . 7 Polymorphisms (5 Amino and 2 Silent)
. . . . . . . . 46T,
. . . . . . . . syn187G (GGt),
. . . . . . . . 273T,
. . . . . . . . 313R,
. . . . . . . . 394I,
. . . . . . . . syn430R (CGg),
. . . . . . . . 467V)
. . . . SwedenGothenburg1_22M_2011_01_16 (
. . . . . . . . GISAID EPI318245
. . . . . . . . 7 Polymorphisms (5 Amino and 2 Silent)
. . . . . . . . 46T,
. . . . . . . . 79P,
. . . . . . . . syn187G (GGt),
. . . . . . . . 313R,
. . . . . . . . 394I,
. . . . . . . . syn430R (CGg),
. . . . . . . . 467V)
Supporting Sequences HA
. . . . Milan18_2011_01_11 (
. . . . . . . . GenBank JF801862
. . . . . . . . 8 Polymorphisms (5 Amino and 3 Silent)
. . . . . . . . HA Truncated before aa11,
. . . . . . . . 59S,
. . . . . . . . syn69E (GAa),
. . . . . . . . 100N,
. . . . . . . . 188T,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . 454N,
. . . . . . . . syn537S (AGc))
. . . . Milan163_2011_01_14 (
. . . . . . . . GenBank JF801878
. . . . . . . . 4 Polymorphisms (3 Amino and 1 Silent)
. . . . . . . . HA Truncated before aa11,
. . . . . . . . 59S,
. . . . . . . . syn69E (GAa),
. . . . . . . . 100N,
. . . . . . . . 188T,
. . . . . . . . HA Truncated after aa327)
. . . . UKEngland334_2010_12_15 (
. . . . . . . . GISAID EPI309641
. . . . . . . . 9 Polymorphisms (6 Amino and 3 Silent)
. . . . . . . . 59S,
. . . . . . . . syn69E (GAa),
. . . . . . . . 100N,
. . . . . . . . 157Q mix wt,
. . . . . . . . 188T,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . 454N,
. . . . . . . . syn537S (AGc))
. . . . UKIreland72392_2010_12_07 (
. . . . . . . . GISAID EPI309663
. . . . . . . . 10 Polymorphisms (7 Amino and 3 Silent)
. . . . . . . . 59S,
. . . . . . . . syn69E (GAa),
. . . . . . . . 100N,
. . . . . . . . 158E mix wt,
. . . . . . . . 163T mix wt,
. . . . . . . . 188T,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . 454N,
. . . . . . . . syn537S (AGc))
. . . . Vladivistok7_2010_12_03 (
. . . . . . . . GISAID EPI306383
. . . . . . . . 12 Polymorphisms (7 Amino and 5 Silent)
. . . . . . . . syn34N (AAt),
. . . . . . . . 85A,
. . . . . . . . 146G,
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . syn215P (CCa),
. . . . . . . . 236I,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . 454N,
. . . . . . . . syn465N (AAt),
. . . . . . . . syn538F (TTt))
. . . . JapanTochigi105_2010_11_20 (
. . . . . . . . GISAID EPI305439
. . . . . . . . 8 Polymorphisms (5 Amino and 3 Silent)
. . . . . . . . syn10Y (TAc),
. . . . . . . . syn34N (AAt),
. . . . . . . . 146G,
. . . . . . . . 166Q mix,
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . 205W mix,
. . . . . . . . syn338G (GGc),
. . . . . . . . HA Truncated after aa347)
. . . . AlabamaAF2073_2010_02_14 (
. . . . . . . . GISAID EPI276240
. . . . . . . . 3 Polymorphisms (3 Amino and 0 Silent)
. . . . . . . . 59S,
. . . . . . . . 269L,
. . . . . . . . 377K,
. . . . . . . . HA Truncated after aa386)
. . . . Hawaii03_2010_02_08 (
. . . . . . . . GISAID EPI278818
. . . . . . . . 4 Polymorphisms (3 Amino and 1 Silent)
. . . . . . . . 38G,
. . . . . . . . 59S,
. . . . . . . . 377K,
. . . . . . . . syn494E (GAa))
. . . . swThailandCU_RA75_2010_01 (
. . . . . . . . GISAID EPI255118
. . . . . . . . 5 Polymorphisms (3 Amino and 2 Silent)
. . . . . . . . 188T,
. . . . . . . . 263D,
. . . . . . . . syn350G (GGg),
. . . . . . . . 414I,
. . . . . . . . syn484N (AAc))
. . . . KoreaDaejeon1871_2009_12_15 (
. . . . . . . . GISAID EPI254654
. . . . . . . . 4 Polymorphisms (4 Amino and 0 Silent)
. . . . . . . . 25R,
. . . . . . . . 59S,
. . . . . . . . 131P,
. . . . . . . . 158E)
. . . . TexasAF2623_2009_12_13 (
. . . . . . . . GISAID EPI281756
. . . . . . . . 6 Polymorphisms (4 Amino and 2 Silent)
. . . . . . . . 57E,
. . . . . . . . 59S,
. . . . . . . . 100N,
. . . . . . . . syn137A (GCt),
. . . . . . . . syn270I (ATc),
. . . . . . . . 377K,
. . . . . . . . HA Truncated after aa386)
Last Updated
2011-06-03
Across 2011-05-30 and 05-31, the Swedish Institute for Infectious Disease Control published 11 pH1N1 sequences at GISAID sampled in a time period spanning January to April 2011 with the majority in February (6). The two deposits merit discussion due to the wide variety of backgrounds demonstrated across such a small population of sequences.
A minimum of 5 Pandemic H1N1 subclades are represented in these 11 Swedish sequences. More than one represented subclade carries revisions that have been associated with laboratory-determined “Low Reactor” status or with illness in previously vaccinated subjects. None of the 11 Swedish sequences fall onto the Pandemic H1N1 Upsilon subclade (pH1N1υ), but several, including one Swedish fatality of a 10 year old male, have crossover polymorphisms previously described in the pH1N1υ superset.
130 polymorphisms (67 amino and 63 silent) are found on these 11 HA segments with 69 distinct HA changes. The 11 NA segments demonstrate 77 polymorphisms (41 amino and 36 silent) with 38 distinct NA changes. 207 total polymorphisms on 11 Swedish sequences (HA + NA) averages to 18.8 changes per sequence. A minimum of 5 subclades with 18 changes per sequence, many at known epitopes (antigenic sites), factors as a significantly difficult target to match with a “single-strain per serotype” vaccine strategy.
Measurable potential for Vaccine Escape increases with circulating diversity as found on these moving targets in Scandinavia and with the clinical and experimental indications of vaccine failure, e.g. HA 128D, HA 158E, et al.
Four of the 11 HA sequences demonstrate 188T of the first pH1N1 emergent nucleotide coding and 2 of those Swedish 188T sequences additionally carry HA 158E in a mixture with wild type. Another 4 of the 11 HA sequences demonstrate 186P with one additionally carrying HA 158E in a mixture with wild type on a background with avian influenza polymorphisms. A concentration of 3 HA 158E revisions in 11 samples mimics the high levels found previously in other Asian and European geographies. The penetration of HA revisions between aa156 and aa159 in Scandinavia is crossing backgrounds and appears to be accelerating.
The fatal case, SwedenMalmoe5_10M_2011_04_21_f, carries 12 HA changes including revision at aa144 (positional to pH1N1υ 144E & 144T) and equality to the pH1N1υ superset at syn287G & 377K. Eight NA changes on the fatal sequence bring the polymorphic total to 20. That total suggests that aggressive viral revision is correlated to fatal and severe cases. These recent high incidences of polymorphism jumping between human subclades appear to follow the dictates of co-location on zoonotic avian sequences.
HA
. . . . SwedenMalmoe5_10M_2011_04_21_f (
. . . . . . . . GISAID EPI318269
. . . . . . . . 12 Polymorphisms (6 Amino and 6 Silent)
. . . . . . . . 137T,
. . . . . . . . 144S,
. . . . . . . . syn163K (AAa),
. . . . . . . . 186P,
. . . . . . . . syn251L (CTg),
. . . . . . . . syn287G (GGg),
. . . . . . . . syn293L (CTt),
. . . . . . . . 298V,
. . . . . . . . syn363G (GGg),
. . . . . . . . 377K,
. . . . . . . . syn474C (TGt),
. . . . . . . . 482I)
. . . . SwedenUppsala6_67F_2011_03_11 (
. . . . . . . . GISAID EPI318263
. . . . . . . . 13 Polymorphisms (6 Amino and 7 Silent)
. . . . . . . . 137T,
. . . . . . . . 144S,
. . . . . . . . syn163K (AAa),
. . . . . . . . 186P,
. . . . . . . . syn251L (CTg),
. . . . . . . . syn287G (GGg),
. . . . . . . . syn293L (CTt),
. . . . . . . . 298V,
. . . . . . . . syn363G (GGg),
. . . . . . . . 377K,
. . . . . . . . syn474C (TGt),
. . . . . . . . syn480E (GAg),
. . . . . . . . 482I)
. . . . SwedenLinkoping7_19F_2011_03_09 (
. . . . . . . . GISAID EPI318260
. . . . . . . . 15 Polymorphisms (7 Amino and 8 Silent)
. . . . . . . . syn42G (GGa),
. . . . . . . . syn47L (CTg),
. . . . . . . . syn58C (TGc),
. . . . . . . . syn82I (ATc),
. . . . . . . . syn93C (TGc),
. . . . . . . . 100N,
. . . . . . . . 141Q,
. . . . . . . . syn170N (AAc),
. . . . . . . . 208K,
. . . . . . . . 219V,
. . . . . . . . 252L,
. . . . . . . . syn307P (CCc),
. . . . . . . . 359A,
. . . . . . . . 377K,
. . . . . . . . syn446K (AAa))
. . . . SwedenStockholm14_32M_2011_02_15 (
. . . . . . . . GISAID EPI318257
. . . . . . . . 18 Polymorphisms (9 Amino and 9 Silent)
. . . . . . . . syn10Y (TAc),
. . . . . . . . syn33V (GTc),
. . . . . . . . syn34N (AAt),
. . . . . . . . syn99I (ATt),
. . . . . . . . 132S,
. . . . . . . . syn139C (TGc),
. . . . . . . . 145R,
. . . . . . . . 146G,
. . . . . . . . 158E mix wt,
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . 454N,
. . . . . . . . syn456L (TTg),
. . . . . . . . syn465N (AAt),
. . . . . . . . 496S,
. . . . . . . . syn538F (TTt))
. . . . SwedenStockholm12_2011_02_13 (
. . . . . . . . GISAID EPI318241
. . . . . . . . 7 Polymorphisms (4 Amino and 3 Silent)
. . . . . . . . 100N,
. . . . . . . . 188T,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . syn431L (tTA),
. . . . . . . . 454N,
. . . . . . . . syn537S (AGc))
. . . . SwedenStockholm13_2011_02_09_sH1N1 (
. . . . . . . . GISAID EPI318247
. . . . . . . . 12 Polymorphisms (5 Amino and 7 Silent)
. . . . . . . . syn41N (AAt),
. . . . . . . . 50I,
. . . . . . . . syn154L (tTA) [swThailandCU_CHK4_2009_01
. . . . . . . . . . . . . . . . . . . . . . . . . with syn69E, 100N, syn154L (CTg),
. . . . . . . . . . . . . . . . . . . . . . . . . 189T, syn215P, 298V,
. . . . . . . . . . . . . . . . . . . . . . . . . syn338G, syn346G, syn388K,
. . . . . . . . . . . . . . . . . . . . . . . . . syn448L (cTA), syn474C, 482I],
. . . . . . . . 158E mix wt,
. . . . . . . . 188T,
. . . . . . . . 259T,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . syn388K (AAa),
. . . . . . . . 415E mix wt,
. . . . . . . . 454N,
. . . . . . . . syn527L (TTa))
. . . . SwedenStockholm10_2011_02_06 (
. . . . . . . . GISAID EPI318238
. . . . . . . . 11 Polymorphisms (7 Amino and 4 Silent)
. . . . . . . . 59S,
. . . . . . . . syn69E (GAa) [swThailandCU_CHK4_2009_01
. . . . . . . . . . . . . . . . . . . . . . . . . with syn69E, 100N, syn154L (CTg),
. . . . . . . . . . . . . . . . . . . . . . . . . 189T, syn215P, 298V,
. . . . . . . . . . . . . . . . . . . . . . . . . syn338G, syn346G, syn388K,
. . . . . . . . . . . . . . . . . . . . . . . . . syn448L (cTA), syn474C, 482I],
. . . . . . . . 100N,
. . . . . . . . 166I [Novel to pH1N1 188T SubClades],
. . . . . . . . 188T,
. . . . . . . . syn215P (CCa) [Vladivistok7_2010_12_03 with 188T],
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . 414I [swThailandCU_RA75_2010_01 with 188T],
. . . . . . . . 454N,
. . . . . . . . syn537S (AGc))
. . . . SwedenStockholm11_2011_02_05 (
. . . . . . . . GISAID EPI318235
. . . . . . . . 7 Polymorphisms (4 Amino and 3 Silent)
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . syn448L (TTg) [swThailandCU_CHK4_2009_01
. . . . . . . . . . . . . . . . . . . . . . . . . with syn69E, 100N, syn154L (CTg),
. . . . . . . . . . . . . . . . . . . . . . . . . 189T, syn215P, 298V,
. . . . . . . . . . . . . . . . . . . . . . . . . syn338G, syn346G, syn388K,
. . . . . . . . . . . . . . . . . . . . . . . . . syn448L (cTA), syn474C, 482I],
. . . . . . . . 454N)
. . . . SwedenMalmoe4_2011_02_13 (
. . . . . . . . GISAID EPI318254
. . . . . . . . 7 Polymorphisms (3 Amino and 4 Silent)
. . . . . . . . syn60I (ATc),
. . . . . . . . 128D,
. . . . . . . . syn218A (GCg),
. . . . . . . . syn273T (ACg),
. . . . . . . . 286E,
. . . . . . . . 377K,
. . . . . . . . syn469E (GAg))
. . . . SwedenUmea1_35x_2011_01_28 (
. . . . . . . . GISAID EPI318266
. . . . . . . . 14 Polymorphisms (7 Amino and 7 Silent)
. . . . . . . . syn98F (TTt),
. . . . . . . . 137T,
. . . . . . . . 144S,
. . . . . . . . syn163K (AAa),
. . . . . . . . 186P,
. . . . . . . . syn251L (CTg),
. . . . . . . . syn287G (GGg),
. . . . . . . . syn293L (CTt),
. . . . . . . . 298V,
. . . . . . . . syn363G (GGg),
. . . . . . . . 377K,
. . . . . . . . 397D mix wt,
. . . . . . . . syn474C (TGt),
. . . . . . . . 482I)
. . . . SwedenGothenburg1_2011_01_16 (
. . . . . . . . GISAID EPI318244
. . . . . . . . 14 Polymorphisms (6 Amino and 8 Silent)
. . . . . . . . 137T,
. . . . . . . . 144S,
. . . . . . . . 158E mix wt,
. . . . . . . . syn163K (AAa),
. . . . . . . . 186P,
. . . . . . . . syn251L (CTg),
. . . . . . . . syn287G (GGg),
. . . . . . . . syn293L (CTt),
. . . . . . . . 298V [swThailandCU_CHK4_2009_01
. . . . . . . . . . . . . . . . . . . . . . . . . with syn69E, 100N, syn154L (CTg),
. . . . . . . . . . . . . . . . . . . . . . . . . 189T, syn215P, 298V,
. . . . . . . . . . . . . . . . . . . . . . . . . syn338G, syn346G, syn388K,
. . . . . . . . . . . . . . . . . . . . . . . . . syn448L (cTA), syn474C, 482I],
. . . . . . . . syn346G (GGa),
. . . . . . . . syn363G (GGg),
. . . . . . . . 377K,
. . . . . . . . syn474C (TGt),
. . . . . . . . 482I)
NA
. . . . SwedenMalmoe5_10M_2011_04_21_f (
. . . . . . . . GISAID EPI318270
. . . . . . . . 8 Polymorphisms (4 Amino and 4 Silent)
. . . . . . . . 46T,
. . . . . . . . syn187G (GGt),
. . . . . . . . 313R,
. . . . . . . . syn336G (GGc),
. . . . . . . . syn370G (GGc),
. . . . . . . . 394I,
. . . . . . . . syn430R (CGg),
. . . . . . . . 467V)
. . . . SwedenUppsala6_67F_2011_03_11 (
. . . . . . . . GISAID EPI318264
. . . . . . . . 7 Polymorphisms (4 Amino and 3 Silent)
. . . . . . . . 46T,
. . . . . . . . syn47E (GAg),
. . . . . . . . syn187G (GGt),
. . . . . . . . 313R,
. . . . . . . . 394I,
. . . . . . . . syn430R (CGg),
. . . . . . . . 467V)
. . . . SwedenLinkoping7_19F_2011_03_09 (
. . . . . . . . GISAID EPI318261
. . . . . . . . 6 Polymorphisms (1 Amino and 5 Silent)
. . . . . . . . syn89S (TCt),
. . . . . . . . syn126P (CCt),
. . . . . . . . syn229S (TCc),
. . . . . . . . syn236G (GGc),
. . . . . . . . syn241V (GTg),
. . . . . . . . 299A)
. . . . SwedenStockholm14_32M_2011_02_15 (
. . . . . . . . GISAID EPI318258
. . . . . . . . 8 Polymorphisms (5 Amino and 3 Silent)
. . . . . . . . 20T,
. . . . . . . . 44S,
. . . . . . . . 119K mix wt,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn378N (AAt))
. . . . SwedenMalmoe4_2011_02_13 (
. . . . . . . . GISAID EPI318255
. . . . . . . . 6 Polymorphisms (4 Amino and 2 Silent)
. . . . . . . . 240I,
. . . . . . . . 264I,
. . . . . . . . syn339S (TCa),
. . . . . . . . syn383T (ACt),
. . . . . . . . 397K,
. . . . . . . . 442I)
. . . . SwedenStockholm12_21F_2011_02_13 (
. . . . . . . . GISAID EPI318242
. . . . . . . . 7 Polymorphisms (4 Amino and 3 Silent)
. . . . . . . . 83M,
. . . . . . . . 173K,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc))
. . . . SwedenStockholm13_2011_02_09 (
. . . . . . . . GISAID EPI318248
. . . . . . . . 9 Polymorphisms (5 Amino and 4 Silent)
. . . . . . . . 20T,
. . . . . . . . 40I,
. . . . . . . . 46T,
. . . . . . . . syn157T (ACt),
. . . . . . . . syn229S (TCc),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa))
. . . . SwedenStockholm10_31F_2011_02_06 (
. . . . . . . . GISAID EPI318239
. . . . . . . . 5 Polymorphisms (2 Amino and 3 Silent)
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc))
. . . . SwedenStockholm11_38F_2011_02_05 (
. . . . . . . . GISAID EPI318236
. . . . . . . . 7 Polymorphisms (2 Amino and 5 Silent)
. . . . . . . . syn162P (CCc),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn398E (GAa),
. . . . . . . . syn416D (GAc))
. . . . SwedenUmea1_35x_2011_01_28 (
. . . . . . . . GISAID EPI318267
. . . . . . . . 7 Polymorphisms (5 Amino and 2 Silent)
. . . . . . . . 46T,
. . . . . . . . syn187G (GGt),
. . . . . . . . 273T,
. . . . . . . . 313R,
. . . . . . . . 394I,
. . . . . . . . syn430R (CGg),
. . . . . . . . 467V)
. . . . SwedenGothenburg1_22M_2011_01_16 (
. . . . . . . . GISAID EPI318245
. . . . . . . . 7 Polymorphisms (5 Amino and 2 Silent)
. . . . . . . . 46T,
. . . . . . . . 79P,
. . . . . . . . syn187G (GGt),
. . . . . . . . 313R,
. . . . . . . . 394I,
. . . . . . . . syn430R (CGg),
. . . . . . . . 467V)
Supporting Sequences HA
. . . . Milan18_2011_01_11 (
. . . . . . . . GenBank JF801862
. . . . . . . . 8 Polymorphisms (5 Amino and 3 Silent)
. . . . . . . . HA Truncated before aa11,
. . . . . . . . 59S,
. . . . . . . . syn69E (GAa),
. . . . . . . . 100N,
. . . . . . . . 188T,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . 454N,
. . . . . . . . syn537S (AGc))
. . . . Milan163_2011_01_14 (
. . . . . . . . GenBank JF801878
. . . . . . . . 4 Polymorphisms (3 Amino and 1 Silent)
. . . . . . . . HA Truncated before aa11,
. . . . . . . . 59S,
. . . . . . . . syn69E (GAa),
. . . . . . . . 100N,
. . . . . . . . 188T,
. . . . . . . . HA Truncated after aa327)
. . . . UKEngland334_2010_12_15 (
. . . . . . . . GISAID EPI309641
. . . . . . . . 9 Polymorphisms (6 Amino and 3 Silent)
. . . . . . . . 59S,
. . . . . . . . syn69E (GAa),
. . . . . . . . 100N,
. . . . . . . . 157Q mix wt,
. . . . . . . . 188T,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . 454N,
. . . . . . . . syn537S (AGc))
. . . . UKIreland72392_2010_12_07 (
. . . . . . . . GISAID EPI309663
. . . . . . . . 10 Polymorphisms (7 Amino and 3 Silent)
. . . . . . . . 59S,
. . . . . . . . syn69E (GAa),
. . . . . . . . 100N,
. . . . . . . . 158E mix wt,
. . . . . . . . 163T mix wt,
. . . . . . . . 188T,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . 454N,
. . . . . . . . syn537S (AGc))
. . . . Vladivistok7_2010_12_03 (
. . . . . . . . GISAID EPI306383
. . . . . . . . 12 Polymorphisms (7 Amino and 5 Silent)
. . . . . . . . syn34N (AAt),
. . . . . . . . 85A,
. . . . . . . . 146G,
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . syn215P (CCa),
. . . . . . . . 236I,
. . . . . . . . syn338G (GGc),
. . . . . . . . 377K,
. . . . . . . . 454N,
. . . . . . . . syn465N (AAt),
. . . . . . . . syn538F (TTt))
. . . . JapanTochigi105_2010_11_20 (
. . . . . . . . GISAID EPI305439
. . . . . . . . 8 Polymorphisms (5 Amino and 3 Silent)
. . . . . . . . syn10Y (TAc),
. . . . . . . . syn34N (AAt),
. . . . . . . . 146G,
. . . . . . . . 166Q mix,
. . . . . . . . 188T,
. . . . . . . . 200T,
. . . . . . . . 205W mix,
. . . . . . . . syn338G (GGc),
. . . . . . . . HA Truncated after aa347)
. . . . AlabamaAF2073_2010_02_14 (
. . . . . . . . GISAID EPI276240
. . . . . . . . 3 Polymorphisms (3 Amino and 0 Silent)
. . . . . . . . 59S,
. . . . . . . . 269L,
. . . . . . . . 377K,
. . . . . . . . HA Truncated after aa386)
. . . . Hawaii03_2010_02_08 (
. . . . . . . . GISAID EPI278818
. . . . . . . . 4 Polymorphisms (3 Amino and 1 Silent)
. . . . . . . . 38G,
. . . . . . . . 59S,
. . . . . . . . 377K,
. . . . . . . . syn494E (GAa))
. . . . swThailandCU_RA75_2010_01 (
. . . . . . . . GISAID EPI255118
. . . . . . . . 5 Polymorphisms (3 Amino and 2 Silent)
. . . . . . . . 188T,
. . . . . . . . 263D,
. . . . . . . . syn350G (GGg),
. . . . . . . . 414I,
. . . . . . . . syn484N (AAc))
. . . . KoreaDaejeon1871_2009_12_15 (
. . . . . . . . GISAID EPI254654
. . . . . . . . 4 Polymorphisms (4 Amino and 0 Silent)
. . . . . . . . 25R,
. . . . . . . . 59S,
. . . . . . . . 131P,
. . . . . . . . 158E)
. . . . TexasAF2623_2009_12_13 (
. . . . . . . . GISAID EPI281756
. . . . . . . . 6 Polymorphisms (4 Amino and 2 Silent)
. . . . . . . . 57E,
. . . . . . . . 59S,
. . . . . . . . 100N,
. . . . . . . . syn137A (GCt),
. . . . . . . . syn270I (ATc),
. . . . . . . . 377K,
. . . . . . . . HA Truncated after aa386)
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