PF11 SNP geographic analysis suggests that the Ukraine cases in the next two weeks may show a very similar genetic pattern to South America in August and the Mediterranean and Adriatic FlightPath in the past 8 weeks.
If the trend toward a higher infectivity of medical personnel continues as reported today of 687 doctors and 1,500 young specialists being ill, we would expect a higher death count in the coming days. Between 0.5% and 1.3% of all doctors in the country are ill (by region). Higher transmissibility is certain.
If a database of 100 sequences were to exist on the Ukraine, accurately cataloging a cross-reference of regions over 14 days of recent death and recovery cases, including major cities, rough expectations would indicate:
HA
225E
in moderate concentration (95% probability) with 206T
206T/225E/300S triplet
potential for introduction (1 sequence) (75% probability)
2E/206T/225E/298V quad combo
potential for appearance in very low count (1 to 2 sequences) (>25% probability)
2E/206T/225G/298V quad combo
potential for introduction (1 sequence) (<10% probability)
225G
potential, but certainly not widespread under current clinical reports (75% probability) with 206T
2E/206S/296H triplet
in low concentration (95% probability)
377K
potential for introduction (1 sequence) (25% probability)
270T
potential for introduction (1 sequence) (7% probability)
261V
potential for appearance in very low count (1 to 3 sequences) (>25% probability)
212 movement
potential for introduction (1 sequence) (7% probability)
208K
potential for introduction (1 sequence) (33% probability)
188/189/190 movement
potential for introduction (1 sequence) (>50% probability)
158E
potential for appearance in very low count (1 to 3 sequences) (>25% probability)
100N
potential for introduction (1 sequence) (>25% probability)
35I
potential for appearance in moderate count (<20% probability)
NA
106I, 248N pairing
potential in very low count (<20% probability)
106I, 248N, 286G triplet
potential for introduction (7% probability until the 8th week of the flashfire)
2009-11-09
2009-11-04
300S with 225E Arises in 6 Year Old Nagasaki Boy during Late August in Japan
Nobuyuki Kobayashi Graduate School of Biomedical Sciences at Nagasaki University deposited 29 HA sequences today at GenBank from July, August and September 2009. These 29 sequences join 3 previous Nagasaki samples for our geographic evaluation. 206T is found on 75% of the area specimens (24 of 32) and is not included in the polymorphism count. 57 total polymorphisms within the HA antigen are spread across 8 residue positions.
2 revisions found only on the Nagasaki backgrounds within ΣPF11 are now conserved.
HA Amino Acid Codings to 3 Novel Polymorphisms and 5 Rare Signals
Nagasaki/HA-10
Nagasaki/HA-17
A/Santiago/2968 (2009-06-26 from 8F) is the singular ΣPF11 peer.
Progenitors may include:
A/red-winged tinamou/Argentina/MP1/2008 (H1N1)
H1N1 Human 2007, 2008, 2009
H1N1 Avian
H1N2 Avian
124I
All Nagasaki except:
Nagasaki/HA-4
Nagasaki/HA-6
Nagasaki/HA-9
Nagasaki/HA-10
Nagasaki/HA-17
Nagasaki/HA-25
Nagasaki/HA-44
Nagasaki/NU-1
Unique to Nagasaki within ΣPF11.
Progenitors may include:
A/goose/Hong Kong/8/1976(H1N1)
A/chicken/Hong Kong/14/1976(H1N1)
225E
Nagasaki/HA-44.
Presently velocitised within recent ΣPF11.
A/Sapporo/1 (2009-06-11) is the singular ΣPF11 peer in Japan.
300S
Nagasaki/HA-44.
Rare to ΣPF11.
Progenitors may include:
H1N1 Swine
H1N1 Avian
307S
All Nagasaki except:
Nagasaki/HA-4
Nagasaki/HA-6
Nagasaki/HA-9
Nagasaki/HA-26
Nagasaki/HA-29
Nagasaki/HA-44
Nagasaki/NU-1
Unique to Nagasaki within ΣPF11.
Progenitor unknown.
447K
Nagasaki/HA-44.
A/Mexico City/70 and A/Italy/132 are the lone ΣPF11 peers.
Progenitor unknown.
513V
Nagasaki/HA-41.
A/Nanjing/1 (2009-06-18) is the singular ΣPF11 peer.
Progenitors may include:
H1N1 Human 2007, 2008, 2009
H1N1 Avian
H1N1 Swine
H1N2 Swine
1918
549K
Nagasaki/HA-10
Nagasaki/HA-14
Novel to ΣPF11.
Progenitor unknown.
2 revisions found only on the Nagasaki backgrounds within ΣPF11 are now conserved.
- 124I is found on 75% of the area specimens (24 of 32 )
- 307S is found on 78% of the area specimens (25 of 32 )
HA Amino Acid Codings to 3 Novel Polymorphisms and 5 Rare Signals
- 40N
- 124I
- 225E
- 300S
- 307S
- 447K
- 513V
- 549K
Nagasaki/HA-10
Nagasaki/HA-17
A/Santiago/2968 (2009-06-26 from 8F) is the singular ΣPF11 peer.
Progenitors may include:
A/red-winged tinamou/Argentina/MP1/2008 (H1N1)
H1N1 Human 2007, 2008, 2009
H1N1 Avian
H1N2 Avian
124I
All Nagasaki except:
Nagasaki/HA-4
Nagasaki/HA-6
Nagasaki/HA-9
Nagasaki/HA-10
Nagasaki/HA-17
Nagasaki/HA-25
Nagasaki/HA-44
Nagasaki/NU-1
Unique to Nagasaki within ΣPF11.
Progenitors may include:
A/goose/Hong Kong/8/1976(H1N1)
A/chicken/Hong Kong/14/1976(H1N1)
225E
Nagasaki/HA-44.
Presently velocitised within recent ΣPF11.
A/Sapporo/1 (2009-06-11) is the singular ΣPF11 peer in Japan.
300S
Nagasaki/HA-44.
Rare to ΣPF11.
Progenitors may include:
H1N1 Swine
H1N1 Avian
307S
All Nagasaki except:
Nagasaki/HA-4
Nagasaki/HA-6
Nagasaki/HA-9
Nagasaki/HA-26
Nagasaki/HA-29
Nagasaki/HA-44
Nagasaki/NU-1
Unique to Nagasaki within ΣPF11.
Progenitor unknown.
447K
Nagasaki/HA-44.
A/Mexico City/70 and A/Italy/132 are the lone ΣPF11 peers.
Progenitor unknown.
513V
Nagasaki/HA-41.
A/Nanjing/1 (2009-06-18) is the singular ΣPF11 peer.
Progenitors may include:
H1N1 Human 2007, 2008, 2009
H1N1 Avian
H1N1 Swine
H1N2 Swine
1918
549K
Nagasaki/HA-10
Nagasaki/HA-14
Novel to ΣPF11.
Progenitor unknown.
2009-11-02
225E Trend Continues in Spain Through October 2009
The Hospital Clinic of Barcelona, Spain continued a strong professional showing this evening by depositing 41 sequences at GenBank covering the month of October 2009, including 14 HA and NA segments. The Spanish officials and medical community must be highly commended for continuing to provide research data of the highest calibre and timeliness during this early stage of the pandemic.
The velocity of change at amino acid residue 225 in the Receptor Binding Domain from October in Spain parallels our report from yesterday on August and September. These samples are contemporary, dating from 2009-10-05 to several in the third week of October (up to 2009-10-22). 6 of 14 specimens (43%) demonstrate 225E paired with 206T. As of this accumulation, Spain shows 37 instances of 225E with no 206S and 3 instances of 225G with 206T.
Additional unique faces also enter ΣPF11 with the Hospital Clinic's October sequences. 26 total polymorphisms within the antigens, HA and NA, spread across 13 amino acid positions generates branching on the Spanish tree in directions that may be suggestive of critical human fitness paths occurring throughout the world.
Of particular interest is the potential cluster:
Clinical information would be very useful in this matter. We are compelled by this Spanish cluster because a very striking HA homology has been circulating in North America since early August. The H8N4 strains may have donated 377K to the H5N1 along the flightpath with a surveillance lag not yet chronicling the event.
HA Amino Acid Codings to 3 Novel Polymorphisms and 8 Rare Signals
CatS1533, CatS1547.
Rare to ΣPF11.
Found in 10 other sequences including recent TamiFlu-Resistant US sequence, A/Texas/47.
Progenitors may include:
H5N1 Avian
H5N1 Human
71G
CatS1478, CatS1587.
CatS1436 and NY80 are the lone ΣPF11 peers.
88L
CatS1533.
Novel to ΣPF11.
89N
CatS1589.
Novel to ΣPF11.
100N
CatS1589.
Rare to ΣPF11.
Found in A/Sao Paulo/55312 and Argentina7953 from the INEI/CII Influenza Virus Sequencing Site.
Progenitors may include:
H1N1 Swine 2009
H1N2 Swine
142T
CatS1574.
CatS1411 is the singular ΣPF11 peer.
225E
CatS1478, CatS1479, CatS1490, CatS1545, CatS1587, CatS1592.
Presently velocitised within recent ΣPF11.
298V
CatS1478, CatS1479, CatS1587.
Unique to Catalonia within ΣPF11.
CatNS2001, CatNS2008, CatS1237, CatS1248, CatS1286, CatS1369, CatS1436.
373H
CatS1525, CatS1589.
Unique to Catalonia within ΣPF11.
CatS1285, CatS1353.
377K
CatS1515, CatS1554.
Novel to ΣPF11.
Progenitors may include:
H8N4 Avian
H6N1 Avian
504N
CatS1525, CatS1589.
A/Gifu-C/67 is the singular ΣPF11 peer.
Progenitors may include:
H1N1 Avian
H1N2 Swine
Neuraminidase Triple Combination
106I, 248D, 286S
All October sequences.
The Neuraminidase displays strong homology with exception in only three sequences.
NA Amino Acid Codings to 2 Novel Polymorphisms
CatS1515.
Identical in HA and MP segments to CatS1554.
Novel to ΣPF11.
Progenitors unknown, but adjacent residue 162 is highly active in:
H5N1 Human
H5N1 Avian
H1N1 Human
H1N1 Avian
H3N2 Human
442I
CatS1525, CatS1589.
Novel to ΣPF11.
Progenitors may include:
H5N1 Human
H5N1 Avian
H1N1 Swine
WSN33
The velocity of change at amino acid residue 225 in the Receptor Binding Domain from October in Spain parallels our report from yesterday on August and September. These samples are contemporary, dating from 2009-10-05 to several in the third week of October (up to 2009-10-22). 6 of 14 specimens (43%) demonstrate 225E paired with 206T. As of this accumulation, Spain shows 37 instances of 225E with no 206S and 3 instances of 225G with 206T.
Additional unique faces also enter ΣPF11 with the Hospital Clinic's October sequences. 26 total polymorphisms within the antigens, HA and NA, spread across 13 amino acid positions generates branching on the Spanish tree in directions that may be suggestive of critical human fitness paths occurring throughout the world.
Of particular interest is the potential cluster:
- A/Catalonia/S1515, HA, NA, MP, sampled on 2009-10-13, 14F
- A/Catalonia/S1554, HA, NA, MP, sampled on 2009-10-20, 1F
Clinical information would be very useful in this matter. We are compelled by this Spanish cluster because a very striking HA homology has been circulating in North America since early August. The H8N4 strains may have donated 377K to the H5N1 along the flightpath with a surveillance lag not yet chronicling the event.
HA Amino Acid Codings to 3 Novel Polymorphisms and 8 Rare Signals
- 35I
- 71G
- 88L
- 89N
- 100N
- 142T
- 225E
- 298V
- 373H
- 504N
CatS1533, CatS1547.
Rare to ΣPF11.
Found in 10 other sequences including recent TamiFlu-Resistant US sequence, A/Texas/47.
Progenitors may include:
H5N1 Avian
H5N1 Human
71G
CatS1478, CatS1587.
CatS1436 and NY80 are the lone ΣPF11 peers.
88L
CatS1533.
Novel to ΣPF11.
89N
CatS1589.
Novel to ΣPF11.
100N
CatS1589.
Rare to ΣPF11.
Found in A/Sao Paulo/55312 and Argentina7953 from the INEI/CII Influenza Virus Sequencing Site.
Progenitors may include:
H1N1 Swine 2009
H1N2 Swine
142T
CatS1574.
CatS1411 is the singular ΣPF11 peer.
225E
CatS1478, CatS1479, CatS1490, CatS1545, CatS1587, CatS1592.
Presently velocitised within recent ΣPF11.
298V
CatS1478, CatS1479, CatS1587.
Unique to Catalonia within ΣPF11.
CatNS2001, CatNS2008, CatS1237, CatS1248, CatS1286, CatS1369, CatS1436.
373H
CatS1525, CatS1589.
Unique to Catalonia within ΣPF11.
CatS1285, CatS1353.
377K
CatS1515, CatS1554.
Novel to ΣPF11.
Progenitors may include:
H8N4 Avian
H6N1 Avian
504N
CatS1525, CatS1589.
A/Gifu-C/67 is the singular ΣPF11 peer.
Progenitors may include:
H1N1 Avian
H1N2 Swine
Neuraminidase Triple Combination
106I, 248D, 286S
All October sequences.
The Neuraminidase displays strong homology with exception in only three sequences.
NA Amino Acid Codings to 2 Novel Polymorphisms
- 161C (synonymous T483C)
- 442I
CatS1515.
Identical in HA and MP segments to CatS1554.
Novel to ΣPF11.
Progenitors unknown, but adjacent residue 162 is highly active in:
H5N1 Human
H5N1 Avian
H1N1 Human
H1N1 Avian
H3N2 Human
442I
CatS1525, CatS1589.
Novel to ΣPF11.
Progenitors may include:
H5N1 Human
H5N1 Avian
H1N1 Swine
WSN33
225E on 45% of Catalonia HA Deposit from August and September
The Hospital Clinic of Barcelona, Spain deposited 21 HA/NA/MP segments at GenBank on Friday. The group as a whole demonstrates significant diversity and the velocity of change at residue 225 in the Receptor Binding Domain is remarkable.
The samples are primarily from August and September, as late as 2009-09-30. One sample is earlier, from July. 9 of 20 specimens (45%) in this deposit that were sampled in August and September demonstrate 225E paired with 206T. As of this accumulation, Spain shows 31 instances of 225E with no 206S and 3 instances of 225G with 206T. Additionally, several unique faces enter ΣPF11 with the Hospital Clinic's latest deposit.
HA Amino Acid Codings to 3 Novel Polymorphisms and 6 Rare Signals
CatS1305, CatS1411, CatS1414, CatS1435.
Rare to ΣPF11.
Found in 6 other sequences including recent TamiFlu-Resistant US sequence, A/Texas/47.
Progenitors may include:
H5N1 Avian
H5N1 Human
71G
CatS1436.
NY80 is the singular ΣPF11 peer.
142T
CatS1411.
Novel to ΣPF11.
188N
CatS1369.
CatS1187 and Niigata700 are the lone ΣPF11 peers.
193G
CatS1384.
Novel to ΣPF11.
225E
CatS1300, CatS1304, CatS1331, CatS1333, CatS1350, CatS1369, CatS1379, CatS1436, CatS1453.
Presently velocitised within recent ΣPF11.
240R
CatS1436.
Novel to ΣPF11.
Progenitors may include:
Zhuhai/790/2008
H1N2 Swine
298V
CatS1369, CatS1436.
Unique to Catalonia within ΣPF11.
CatNS2001, CatNS2008, CatS1237, CatS1248, CatS1286.
373H
CatS1353.
Unique to Catalonia within ΣPF11.
CatS1285.
Neuraminidase Triple Combination
106I, 248D, 286S 20 Sequences
106V, 248D, 286S CatS1369.
The pattern shown by CatS1369 is found in 4 other instances within ΣPF11. Three of those were very early in the pandemic and the most recent is A/Toronto/R8564 from a 7F in early July.
This Neuraminidase group displays some variety with exception in three sequences.
NA Amino Acid Codings to 4 Polymorphisms
CatS1402.
369T
CatS1307, CatS1402.
386D
CatS1384.
395R
CatS1402.
The samples are primarily from August and September, as late as 2009-09-30. One sample is earlier, from July. 9 of 20 specimens (45%) in this deposit that were sampled in August and September demonstrate 225E paired with 206T. As of this accumulation, Spain shows 31 instances of 225E with no 206S and 3 instances of 225G with 206T. Additionally, several unique faces enter ΣPF11 with the Hospital Clinic's latest deposit.
HA Amino Acid Codings to 3 Novel Polymorphisms and 6 Rare Signals
- 35I
- 71G
- 142T
- 188N
- 193G
- 225E
- 240R
- 298V
- 373H
CatS1305, CatS1411, CatS1414, CatS1435.
Rare to ΣPF11.
Found in 6 other sequences including recent TamiFlu-Resistant US sequence, A/Texas/47.
Progenitors may include:
H5N1 Avian
H5N1 Human
71G
CatS1436.
NY80 is the singular ΣPF11 peer.
142T
CatS1411.
Novel to ΣPF11.
188N
CatS1369.
CatS1187 and Niigata700 are the lone ΣPF11 peers.
193G
CatS1384.
Novel to ΣPF11.
225E
CatS1300, CatS1304, CatS1331, CatS1333, CatS1350, CatS1369, CatS1379, CatS1436, CatS1453.
Presently velocitised within recent ΣPF11.
240R
CatS1436.
Novel to ΣPF11.
Progenitors may include:
Zhuhai/790/2008
H1N2 Swine
298V
CatS1369, CatS1436.
Unique to Catalonia within ΣPF11.
CatNS2001, CatNS2008, CatS1237, CatS1248, CatS1286.
373H
CatS1353.
Unique to Catalonia within ΣPF11.
CatS1285.
Neuraminidase Triple Combination
106I, 248D, 286S 20 Sequences
106V, 248D, 286S CatS1369.
The pattern shown by CatS1369 is found in 4 other instances within ΣPF11. Three of those were very early in the pandemic and the most recent is A/Toronto/R8564 from a 7F in early July.
This Neuraminidase group displays some variety with exception in three sequences.
NA Amino Acid Codings to 4 Polymorphisms
- 321V
- 369T
- 386D
- 395R
CatS1402.
369T
CatS1307, CatS1402.
386D
CatS1384.
395R
CatS1402.
2009-10-30
Matching Pair of Human-Fit NA Novelty Emerges Independently in Two Distinct Locales during August 2009
The University of Padova deposited 23 Neuraminidase segments at GenBank yesterday. One particularly merits discussion. We were keyed to the sequence by the rare 106I and 248N human pairing, but even more human fitness acquisition was at work upon review. The NA of A/Italy/180, sampled in August 2009 from a 47M, brings another unique face into ΣPF11.
NA Amino Acid Codings to 1 Novel Polymorphism and 2 Independent Co-Emergent Signals
Neuraminidase Triple Combination
106I, 248N, 286S
Only 25 sequences currently match the 146 amino acids from 106I to 248N, including the Italy134 sequence recently profiled demonstrating the NA Triple Combination herald for Pandemic 2.0.
This new Italian sequence is a marvel in itself, but the argument against random mutation gains strength upon a similar and apparently independent co-emergence. Two perfectly novel introductions paired onto two divergent backgrounds in two different geographies suggest a randomness redundancy.
A/Catalonia/S1276, sampled 2009-08-19 from a 13F, also demonstrates two of the three novel introductions, but onto a separate NA background. CatS1276 is a perfect nucleotide match to Italy180 except at 742G generating 248D (1216 of 1217 aligned residues). Like many of the Catalonia sequences, the initial 47 amino acids of CatS1276 are absent or we might find the 45K there as well. Even without the full sequence, CatS1276 is unique and stand-alone within ΣPF11 due to the swine 248D conjoined with 386D and C1276T.
45K
Novel to ΣPF11.
Progenitors may include:
A/Washington/03/2009 H1N1 with HA 230I & NA 386D, syn426L
A/New Jersey/30/2008 H1N1 with HA 230I & NA 386D, syn426L
A/Thailand/271/2005 H1N1 with HA 225G, 261N, 263D, 270T & NA:45K, syn346V
386D
CatS1276 is the singular ΣPF11 peer.
Progenitors may include:
Seasonal H1N1 2005, 2006, 2007, 2008 and 2009 (Consensus)
Avian H1N1
syn426L
CatS1276 is the singular ΣPF11 peer.
Seasonal H1N1 2005, 2006, 2007, 2008 and 2009 (Extensive)
Swine H1N1 1990-1999
WSN33
Paired genetic introductions onto disparate backgrounds are not a spline for randomness. Perhaps a less random examination of the database at hand would provide additional observational evidence for a new school of logic? Without question, human-fit genetics from previous Seasonal H1N1 and H3N2 are being gained by the Hydra pandemic strains. In this case, the sub-segment acquisitions are precise and clear.
NA Amino Acid Codings to 1 Novel Polymorphism and 2 Independent Co-Emergent Signals
- 45K
- 386D
- 426L (synonymous C1276T)
Neuraminidase Triple Combination
106I, 248N, 286S
Only 25 sequences currently match the 146 amino acids from 106I to 248N, including the Italy134 sequence recently profiled demonstrating the NA Triple Combination herald for Pandemic 2.0.
This new Italian sequence is a marvel in itself, but the argument against random mutation gains strength upon a similar and apparently independent co-emergence. Two perfectly novel introductions paired onto two divergent backgrounds in two different geographies suggest a randomness redundancy.
A/Catalonia/S1276, sampled 2009-08-19 from a 13F, also demonstrates two of the three novel introductions, but onto a separate NA background. CatS1276 is a perfect nucleotide match to Italy180 except at 742G generating 248D (1216 of 1217 aligned residues). Like many of the Catalonia sequences, the initial 47 amino acids of CatS1276 are absent or we might find the 45K there as well. Even without the full sequence, CatS1276 is unique and stand-alone within ΣPF11 due to the swine 248D conjoined with 386D and C1276T.
45K
Novel to ΣPF11.
Progenitors may include:
A/Washington/03/2009 H1N1 with HA 230I & NA 386D, syn426L
A/New Jersey/30/2008 H1N1 with HA 230I & NA 386D, syn426L
A/Thailand/271/2005 H1N1 with HA 225G, 261N, 263D, 270T & NA:45K, syn346V
386D
CatS1276 is the singular ΣPF11 peer.
Progenitors may include:
Seasonal H1N1 2005, 2006, 2007, 2008 and 2009 (Consensus)
Avian H1N1
syn426L
CatS1276 is the singular ΣPF11 peer.
Seasonal H1N1 2005, 2006, 2007, 2008 and 2009 (Extensive)
Swine H1N1 1990-1999
WSN33
Paired genetic introductions onto disparate backgrounds are not a spline for randomness. Perhaps a less random examination of the database at hand would provide additional observational evidence for a new school of logic? Without question, human-fit genetics from previous Seasonal H1N1 and H3N2 are being gained by the Hydra pandemic strains. In this case, the sub-segment acquisitions are precise and clear.
Labels:
386D,
426L,
45K,
Human-Fit,
Hydra Effect,
NA Dual Combination,
NA Triple Combination
2009-10-28
PB2 Changes in Multiple Japanese Sequences downstream of known Virulence Factor
Japanese PB2 sequences deposited today at GenBank carry novel introductions to ΣPF11 and to human H1N1. A concern comes into play when the PF11 PB2 segment, of avian origin, acquires genetic material from human-fit Seasonal Influenza.
A/Niigata/690, sampled 2009-06-15, carries 702R, unique to ΣPF11 and found previously in 1918, LabVir PuertoRico8, Seasonal H1N1 and Seasonal H3N2.
A/Hiroshima/220, sampled 2009-07-03, carries 704H, unique to ΣPF11, to human H1N1 and to human H3N2. Progenitor unknown.
These two PB2 polymorphisms are adjacent to a known Virulence Factor. Note that the 701N discussed in the Palese study is found on Seasonal H1N1, Seasonal H3N2 and on human H5N1. Apparently H3N2 may be playing a significant role as a recombination donor to PF11.
As you will see from the following listing, PB2 is active at this area in ΣPF11.
698D - California06
700K - Osaka180 TamiFlu Resistant with NA Pairing of 106I and 248N
701N - Shanghai71T_May with 627K
702T - NJ02
702R - Niigata690
703X - WA29 TamiFlu Resistant
703K - Shanghai71T_May with 627K, Shanghai71T_June
704H - Hiroshima220
714R - Hyogo2
720K - Nebraska02
The previously published segment 4 (HA) of Hiroshima220 shows 130E in a domain that may yield antigenic diversity. Notice that another human Virulence Factor 225G from the HA RBD has been demonstrated in the locale of Hiroshima.
Further analysis will be conducted as time permits.
A/Niigata/690, sampled 2009-06-15, carries 702R, unique to ΣPF11 and found previously in 1918, LabVir PuertoRico8, Seasonal H1N1 and Seasonal H3N2.
A/Hiroshima/220, sampled 2009-07-03, carries 704H, unique to ΣPF11, to human H1N1 and to human H3N2. Progenitor unknown.
These two PB2 polymorphisms are adjacent to a known Virulence Factor. Note that the 701N discussed in the Palese study is found on Seasonal H1N1, Seasonal H3N2 and on human H5N1. Apparently H3N2 may be playing a significant role as a recombination donor to PF11.
As you will see from the following listing, PB2 is active at this area in ΣPF11.
698D - California06
700K - Osaka180 TamiFlu Resistant with NA Pairing of 106I and 248N
701N - Shanghai71T_May with 627K
702T - NJ02
702R - Niigata690
703X - WA29 TamiFlu Resistant
703K - Shanghai71T_May with 627K, Shanghai71T_June
704H - Hiroshima220
714R - Hyogo2
720K - Nebraska02
The previously published segment 4 (HA) of Hiroshima220 shows 130E in a domain that may yield antigenic diversity. Notice that another human Virulence Factor 225G from the HA RBD has been demonstrated in the locale of Hiroshima.
Further analysis will be conducted as time permits.
Labels:
702R,
704H,
Japan,
PB2,
Virulence Factor
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.
Labels:
106I,
248N,
256L,
286G,
Adriatic Sea,
Antigenic Diversity,
Balkan,
Black Sea,
Caspian Sea,
Catalyst,
Human-Fit,
Italy,
NA Triple Combination,
PF11 Omega
2009-10-20
Nagasaki brings Novel HA Introductions into PF11 with 124I and 307S
A Japanese sequence from Nagasaki was published at GenBank today with the antigen Hemagglutinin only. The sample was collected in July 2009 from a 4 year old female child and represents another unique face to ΣPF11.
HA Amino Acid Codings to 2 Novel Polymorphisms
124I
Novel to ΣPF11.
Progenitors may include:
A/goose/Hong Kong/8/1976(H1N1)
A/chicken/Hong Kong/14/1976(H1N1)
Movement is common at this residue in human and avian H5N1 and swine H1N1
307S
Novel to ΣPF11.
Progenitors unknown.
HA Amino Acid Codings to 2 Novel Polymorphisms
- 124I
- 307S
124I
Novel to ΣPF11.
Progenitors may include:
A/goose/Hong Kong/8/1976(H1N1)
A/chicken/Hong Kong/14/1976(H1N1)
Movement is common at this residue in human and avian H5N1 and swine H1N1
307S
Novel to ΣPF11.
Progenitors unknown.
2009-10-19
225G in Receptor Binding Domain Traveled to China without Vaccine Pairing of 206S
The expected Hydra Effect on Hemagglutinin patterns are being validated with the latest sequence deposits. Multiple antigenic heads continue to arise within single geographic areas while the march from Southern Hemisphere winter strains (May-July 2009) into the Northern Hemisphere ΣPF11 lays distinct markers.
Two sequences today from China carry the Receptor Binding Domain polymorphism coding for 225G similar to the fatal cases during the South American winter. These sequences represent the first movement of 225G into China and the second into Asia after Hiroshima201, although we have observed 225E in one instance, Changsha78.
This incursion of 225G makes Zhejiang Province one of very few geographic locales to represent both vaccine RBD polymorphisms as 226R was demonstrated mid-summer in A/Zhejiang/DTID-ZJU01/2009.
Let's examine the new Yiwu HA segments for this analysis:
These two Zhejiang province cases were sampled in September making the sequences contemporary for evaluation of the genetic acquisition cycle pertinent to North America today. Each case continues the recent affinity of 206T with 225G. Nine of fourteen instances of 225G on record within ΣPF11 are paired with 206T and only one isolated sequence after April has 206S in the pairing. You will note that the live vaccine is based on an early finding in Texas and Mexico (Texas05 pairing of 206S / 225G). The current sequences continue to demonstrate a directional movement away from those four early Texas and Mexican strains from April.
The Yiwu11 case, 41F, is specifically noted as having "severe symptoms". Confidence is increased that these sequences are valid due to independent verification. The two sequences were managed from separate labs though the hosts were apparently from the same city, Yiwu, and suffered during the same time frame.
Each of the two HA sequences represent a novel introduction into ΣPF11. Yiwu11's closest GenBank match is 1758 of 1774 nucleotides and ZJU02's closest match is Yiwu11. The two sequences are an exact nucleotide match (1759/1759) at all alignable positions (sequence truncation at Yiwu11 head and ZJU02 tail), potentially representing perfect transmission in Asia of 225G. The Catalonia sequences from Spain in early August initiated the first and only previously recorded perfect segment transmission of a 206T / 225G pairing. The Brasil deaths share amino acid homology, but varied at a silent SNP coding for Lysine at residue 222 (222K).
If a cluster is in effect with these two sequences, then we may be observing a foundational, well-passaged, human-fit strain in the Northern Hemisphere heralding Pandemic 2.0 Influenza. Only time will tell.
A correlation is also emerging in consideration of geography and population ethnicity with nine of the fourteen 225G cases in areas with a substantial Hispanic population. The ethnic profiles of the individual cases are not identified. Yiwu is a burgeoning commodities trading area with a substantial immigrant population including import/export workers from South America. If we note that NY and Georgia have Hispanic populations, then only Hiroshima remains as a potential non-Hispanic area. At any rate, the correlation of 225G to areas with Hispanic human genotypes bears scrutiny for pathogen-host interaction at the genetic level.
Recall that other human-fit genetic advances are recorded in the Zhejiang Province recently. Of minor note, the Neuraminidase segments of Yiwu11 and ZJU02 are also novel to the reservoir though the amino acid levels match widely. A third base SNP that merits attention has now spanned from the original introduction in A/Netherlands/602 to ZJU02, A408G coding at residue 136 for a synonymous Glutamine (136Q). Movement at this amino acid position is implicated in Relenza resistence (136K), though the synonymous change from the Netherlands and Zhejiang is not accorded trait enhancement in the literature.
This advancing Antigenic Diversity and movement of 225G separated from the 206S into a highly populated country prior to winter should generate a call for wider surveillance and more rapid deposition of sequences.
Two sequences today from China carry the Receptor Binding Domain polymorphism coding for 225G similar to the fatal cases during the South American winter. These sequences represent the first movement of 225G into China and the second into Asia after Hiroshima201, although we have observed 225E in one instance, Changsha78.
This incursion of 225G makes Zhejiang Province one of very few geographic locales to represent both vaccine RBD polymorphisms as 226R was demonstrated mid-summer in A/Zhejiang/DTID-ZJU01/2009.
Let's examine the new Yiwu HA segments for this analysis:
These two Zhejiang province cases were sampled in September making the sequences contemporary for evaluation of the genetic acquisition cycle pertinent to North America today. Each case continues the recent affinity of 206T with 225G. Nine of fourteen instances of 225G on record within ΣPF11 are paired with 206T and only one isolated sequence after April has 206S in the pairing. You will note that the live vaccine is based on an early finding in Texas and Mexico (Texas05 pairing of 206S / 225G). The current sequences continue to demonstrate a directional movement away from those four early Texas and Mexican strains from April.
The Yiwu11 case, 41F, is specifically noted as having "severe symptoms". Confidence is increased that these sequences are valid due to independent verification. The two sequences were managed from separate labs though the hosts were apparently from the same city, Yiwu, and suffered during the same time frame.
Each of the two HA sequences represent a novel introduction into ΣPF11. Yiwu11's closest GenBank match is 1758 of 1774 nucleotides and ZJU02's closest match is Yiwu11. The two sequences are an exact nucleotide match (1759/1759) at all alignable positions (sequence truncation at Yiwu11 head and ZJU02 tail), potentially representing perfect transmission in Asia of 225G. The Catalonia sequences from Spain in early August initiated the first and only previously recorded perfect segment transmission of a 206T / 225G pairing. The Brasil deaths share amino acid homology, but varied at a silent SNP coding for Lysine at residue 222 (222K).
If a cluster is in effect with these two sequences, then we may be observing a foundational, well-passaged, human-fit strain in the Northern Hemisphere heralding Pandemic 2.0 Influenza. Only time will tell.
A correlation is also emerging in consideration of geography and population ethnicity with nine of the fourteen 225G cases in areas with a substantial Hispanic population. The ethnic profiles of the individual cases are not identified. Yiwu is a burgeoning commodities trading area with a substantial immigrant population including import/export workers from South America. If we note that NY and Georgia have Hispanic populations, then only Hiroshima remains as a potential non-Hispanic area. At any rate, the correlation of 225G to areas with Hispanic human genotypes bears scrutiny for pathogen-host interaction at the genetic level.
Recall that other human-fit genetic advances are recorded in the Zhejiang Province recently. Of minor note, the Neuraminidase segments of Yiwu11 and ZJU02 are also novel to the reservoir though the amino acid levels match widely. A third base SNP that merits attention has now spanned from the original introduction in A/Netherlands/602 to ZJU02, A408G coding at residue 136 for a synonymous Glutamine (136Q). Movement at this amino acid position is implicated in Relenza resistence (136K), though the synonymous change from the Netherlands and Zhejiang is not accorded trait enhancement in the literature.
This advancing Antigenic Diversity and movement of 225G separated from the 206S into a highly populated country prior to winter should generate a call for wider surveillance and more rapid deposition of sequences.
Labels:
206S,
206T,
225G,
Antigenic Diversity,
China,
Hispanic,
Pandemic 2.0,
Pandemic Influenza 2.0
2009-10-16
Iran deposits Sequences with H5N1 Fingerprints
The first PF11 sequences from Iran were published at GenBank on 2009-10-13. The three Neuraminidase segments were sampled between 2009-07-27 and 2009-07-30. Each of the three brings a unique face into ΣPF11.
Though these sequences all share a starting polymorphism, each develops one or more additional novel antigenic revisions. The build pattern is suggestive that surveillance efforts are lacking. The database contains no intermediate forms that would allow us to observe the individual genetic acquisitions from the birds, pigs and humans as they occurred to build this minimum two step magnetism from H5N1 and H5N2 onto the Iran H1N1 background.
NA Amino Acid Codings to 5 Novel Polymorphisms and 1 Singular Signal
4K
Novel to ΣPF11.
100% of the Iranian sequences carry Lysine at the fourth amino acid position (4K), a novel finding in the pandemic reservoir that appears to be only recorded in two earlier sequences.
Progenitors may include:
A/duck/Eastern China/06/2000 (H5N2)
A/Fort Warren/1/1950 (H1N1)
74L
Bogota0466N is the singular ΣPF11 instance.
Lorestan1599
Progenitors may include:
red-winged tinamou/Argentina/MP1/2008 H1N1
with HA 225G, 277N, 286H, 298V / NA 106I, 248N, 286G
81G
Novel to ΣPF11.
Lorestan1599
Progenitor unknown.
syn346V
Novel to ΣPF11.
Ghom1550
Progenitors may include:
A/Thailand/271/2005 (H1N1) with NA 45K & HA 225G, 261N, 263D, 264P and 270T, also manages to carry the silent NA:A1038G coding for a synonymous Valine at residue 346 on the Neuramindase (346V) of Ghom1550. This silent change is found across many serotypes and primarily spans Avian and Swine species. Influenza Flux may be at work.
452S
Novel to ΣPF11.
Khorasan1583
Progenitor unknown.
454S
Novel to ΣPF11.
Khorasan1583
Progenitors may include:
H5N1 2009 Human Toddler passage Egypt
H5N1 2009 Avian Worldwide
H1N1 2005 Human Iowa swine worker (IA/CEID23/2005)
H1N1 NC swine 36883, HK swine NS1659
Neuraminidase Quadruple Combination
106I, 248D, 275H, 286S
Though these sequences all share a starting polymorphism, each develops one or more additional novel antigenic revisions. The build pattern is suggestive that surveillance efforts are lacking. The database contains no intermediate forms that would allow us to observe the individual genetic acquisitions from the birds, pigs and humans as they occurred to build this minimum two step magnetism from H5N1 and H5N2 onto the Iran H1N1 background.
NA Amino Acid Codings to 5 Novel Polymorphisms and 1 Singular Signal
- 4K
- 74L
- 81G
- 346V (synonymous A1038G)
- 452S
- 454S
4K
Novel to ΣPF11.
100% of the Iranian sequences carry Lysine at the fourth amino acid position (4K), a novel finding in the pandemic reservoir that appears to be only recorded in two earlier sequences.
Progenitors may include:
A/duck/Eastern China/06/2000 (H5N2)
A/Fort Warren/1/1950 (H1N1)
74L
Bogota0466N is the singular ΣPF11 instance.
Lorestan1599
Progenitors may include:
red-winged tinamou/Argentina/MP1/2008 H1N1
with HA 225G, 277N, 286H, 298V / NA 106I, 248N, 286G
81G
Novel to ΣPF11.
Lorestan1599
Progenitor unknown.
syn346V
Novel to ΣPF11.
Ghom1550
Progenitors may include:
A/Thailand/271/2005 (H1N1) with NA 45K & HA 225G, 261N, 263D, 264P and 270T, also manages to carry the silent NA:A1038G coding for a synonymous Valine at residue 346 on the Neuramindase (346V) of Ghom1550. This silent change is found across many serotypes and primarily spans Avian and Swine species. Influenza Flux may be at work.
452S
Novel to ΣPF11.
Khorasan1583
Progenitor unknown.
454S
Novel to ΣPF11.
Khorasan1583
Progenitors may include:
H5N1 2009 Human Toddler passage Egypt
H5N1 2009 Avian Worldwide
H1N1 2005 Human Iowa swine worker (IA/CEID23/2005)
H1N1 NC swine 36883, HK swine NS1659
Neuraminidase Quadruple Combination
106I, 248D, 275H, 286S
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