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)
Showing posts with label Italy. Show all posts
Showing posts with label Italy. Show all posts
2009-10-23
Potential Catalyst for Pandemic 2.0 Emerges in Italy during July
During the Summer of 2009, an unsuspecting twelve year old boy in Veneto, Italy may have become the host of an influenza strain that is now setting the Pandemic 2.0 stage.
The Northern Italian region of Veneto has a population nearing 5 million and hosts 60 million tourists each year with many passing through the canals of the capital, Venice. The Laguna Veneta is the largest wetland in the Mediterrean (340mi2 / 550km2) and the delta serves a wide range of migratory bird species.
The University of Padova lab deposited 24 Neuraminidase (N1) sequences today from Italy sampled during July 2009 (Pandemic 1.5) bringing the total number of Italian NA segments on file to 26. Antigenic diversity is observed in the Italian sequences, several with novel introductions, but the point variations are not our primary interest in this very important deposit.
One sequence from the Padova lab signals the first recorded instance of a key transition for this pandemic. The NA Triple Combination may mark an axis or inflection point for PF11. A/Italy/134, from a student (12M) in Veneto, demonstrates a match to Seasonal Influenza in a permutation of 3 key markers that we have anticipated as a potential catalyst to Pandemic 2.0.
A Balkan emergence had generated the highest probability in our research with the Italian peninsula and bounding northern states ranking as "Very Probable". Few sequences have been made available to evaluate the Balkan states during this pandemic, so we cannot determine if the recombinations occurred in that area as well as in Italy. Emergence was expected within a 250 mile radius (400km) of a significant body of water, particularly the Adriatic Sea, the Black Sea or the western boundary of the Caspian Sea. Of course, we may be searching for our keys under the streetlamp. So little surveillance is surfaced at this point that rough estimates are the maximum any lab may produce.
In Italy134, this coalescing set of 3 human-fit markers, predicted by our research in mid-May, emerged during the summer, recombined as expected onto the swine N1 background. As you may observe from the positional study, this sequence may have required two or more in situ polymorphisms from consensus within this geography to gain these genetics. In the estimation of our research team, random mutation is a less than stellar explanation. Human-fit Seasonal Influenza and ΣPF11 now have much more in common as ΣPF11 moves into tighter conformation potentially gaining trait enhancements.
Neuraminidase Triple Combination
106I, 248N, 286G : Italy134
106I, 248N, 286G : Seasonal Influenza 2005, 2006, 2007, 2008, 2009
106I, 248N, 286G : H5N1 (Avian, Human), H1N1 (Avian, Swine)
106I, 248N, 286G : 1918 Brevig Mission
This July sequence lays additional groundwork for attractant donations from candidates in previously observed donor serotypes.
Few Italian points of comparison are available prior to this large NA deposit. Of the two, NA Italy05 is unremarkable for this study and NA Italy127 is quite remarkable due to temporal and geographic proximity, as you will see in the Italian permutation discussion. We also note that the Hemagglutinin segments so prolifically available from Italy demonstrate exceptional variance (20 major polymorphisms from 34 Sequences). These Hemagglutinin amino acid revisions include, but are not limited to, 137T, 199N, 200T, 219T, 225E (4), 244I, 261G (2), 277E, 296H (4) and 300S (2). NA variance is correlated with HA variance in ΣPF11.
Antigenic Diversity, even within the sparse 26 Italian NA sequences is observable if only upon reviewing the four permutations of the Neuraminidase Triple Combination.
106I, 248N, 286G : Italy134 from Veneto, sampled 2009-07
106I, 248N, 286S : Italy127 from Veneto, sampled 2009-06-17, 256L (H3N2, H5N1 Avian)
106I, 248D, 286S : 23 Sequences, including Italy05 from May 2009
106V, 248N, 286S : Italy149
Italy134 is most similar at the protein (468/469) and nucleotide (1407/1410) levels to two different groups of sequences: the NA 286G bearing group from Canada (5 of 6 Sequences) and the Asian group (with Louisiana03) carrying the rare PF11 dual combination of 106I and 248N (20 sequences). The Russian Almati01 and Ekaterinburg01 round out the set with the 106I/248N pairing, but vary at an additional amino acid from Italy134. Only 24 sequences at GenBank carry the PF11 amino acid homology between 106I and 248N.
Until PF11Ω is achieved, Influenza Flux will continue to vary the virulence and transmute the transmissibility at individual geographies. Future scrutiny of the NA permutations discussed here is merited. Bear in mind that the current reservoir, even with this instance of tighter human coupling, remains hobbled by transitional genetics. Fitness determination of this Seasonal NA Triple Combination on the swine N1 background of PF11 remains to be determined at such time as sequences are surfaced.
The Northern Italian region of Veneto has a population nearing 5 million and hosts 60 million tourists each year with many passing through the canals of the capital, Venice. The Laguna Veneta is the largest wetland in the Mediterrean (340mi2 / 550km2) and the delta serves a wide range of migratory bird species.
The University of Padova lab deposited 24 Neuraminidase (N1) sequences today from Italy sampled during July 2009 (Pandemic 1.5) bringing the total number of Italian NA segments on file to 26. Antigenic diversity is observed in the Italian sequences, several with novel introductions, but the point variations are not our primary interest in this very important deposit.
One sequence from the Padova lab signals the first recorded instance of a key transition for this pandemic. The NA Triple Combination may mark an axis or inflection point for PF11. A/Italy/134, from a student (12M) in Veneto, demonstrates a match to Seasonal Influenza in a permutation of 3 key markers that we have anticipated as a potential catalyst to Pandemic 2.0.
A Balkan emergence had generated the highest probability in our research with the Italian peninsula and bounding northern states ranking as "Very Probable". Few sequences have been made available to evaluate the Balkan states during this pandemic, so we cannot determine if the recombinations occurred in that area as well as in Italy. Emergence was expected within a 250 mile radius (400km) of a significant body of water, particularly the Adriatic Sea, the Black Sea or the western boundary of the Caspian Sea. Of course, we may be searching for our keys under the streetlamp. So little surveillance is surfaced at this point that rough estimates are the maximum any lab may produce.
In Italy134, this coalescing set of 3 human-fit markers, predicted by our research in mid-May, emerged during the summer, recombined as expected onto the swine N1 background. As you may observe from the positional study, this sequence may have required two or more in situ polymorphisms from consensus within this geography to gain these genetics. In the estimation of our research team, random mutation is a less than stellar explanation. Human-fit Seasonal Influenza and ΣPF11 now have much more in common as ΣPF11 moves into tighter conformation potentially gaining trait enhancements.
Neuraminidase Triple Combination
106I, 248N, 286G : Italy134
106I, 248N, 286G : Seasonal Influenza 2005, 2006, 2007, 2008, 2009
106I, 248N, 286G : H5N1 (Avian, Human), H1N1 (Avian, Swine)
106I, 248N, 286G : 1918 Brevig Mission
This July sequence lays additional groundwork for attractant donations from candidates in previously observed donor serotypes.
Few Italian points of comparison are available prior to this large NA deposit. Of the two, NA Italy05 is unremarkable for this study and NA Italy127 is quite remarkable due to temporal and geographic proximity, as you will see in the Italian permutation discussion. We also note that the Hemagglutinin segments so prolifically available from Italy demonstrate exceptional variance (20 major polymorphisms from 34 Sequences). These Hemagglutinin amino acid revisions include, but are not limited to, 137T, 199N, 200T, 219T, 225E (4), 244I, 261G (2), 277E, 296H (4) and 300S (2). NA variance is correlated with HA variance in ΣPF11.
Antigenic Diversity, even within the sparse 26 Italian NA sequences is observable if only upon reviewing the four permutations of the Neuraminidase Triple Combination.
106I, 248N, 286G : Italy134 from Veneto, sampled 2009-07
106I, 248N, 286S : Italy127 from Veneto, sampled 2009-06-17, 256L (H3N2, H5N1 Avian)
106I, 248D, 286S : 23 Sequences, including Italy05 from May 2009
106V, 248N, 286S : Italy149
Italy134 is most similar at the protein (468/469) and nucleotide (1407/1410) levels to two different groups of sequences: the NA 286G bearing group from Canada (5 of 6 Sequences) and the Asian group (with Louisiana03) carrying the rare PF11 dual combination of 106I and 248N (20 sequences). The Russian Almati01 and Ekaterinburg01 round out the set with the 106I/248N pairing, but vary at an additional amino acid from Italy134. Only 24 sequences at GenBank carry the PF11 amino acid homology between 106I and 248N.
Until PF11Ω is achieved, Influenza Flux will continue to vary the virulence and transmute the transmissibility at individual geographies. Future scrutiny of the NA permutations discussed here is merited. Bear in mind that the current reservoir, even with this instance of tighter human coupling, remains hobbled by transitional genetics. Fitness determination of this Seasonal NA Triple Combination on the swine N1 background of PF11 remains to be determined at such time as sequences are surfaced.
2009-09-10
Italy HA Homology to two TamiFlu-Resistant Asian Specimens
- A/Italy/130, sampled 2009-06-10 from a 43M
No segment 6 (Neuraminidase/N1) is published for any of the 6 Italian sequences released today, including Italy130; ergo, TamiFlu-Resistance cannot be invalidated by data.
Absence of data is apparently being commissioned as the new art form?
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