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 pH1N1_υ 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)

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