| EU516201.1 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=Nucleotide&list_uids=168827354&dopt=GenBank&RID=WURX8KSX014&log$=nucltop&blast_rank=3) | Influenza A virus (A/New Jersey/16/2007(H1N1)) segment 6 neuraminidase (NA) gene, complete cds | 26.3 (http://www.ncbi.nlm.nih.gov/blast/Blast.cgi#168827354) | 26.3 | 100% | 571 | 100% | |
| EU516200.1 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=Nucleotide&list_uids=168827352&dopt=GenBank&RID=WURX8KSX014&log$=nucltop&blast_rank=4) | Influenza A virus (A/Illinois/10/2007(H1N1)) segment 6 neuraminidase (NA) gene, complete cds | 26.3 (http://www.ncbi.nlm.nih.gov/blast/Blast.cgi#168827352) | 26.3 | 100% | 571 | 100% | |
| EU516199.1 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=Nucleotide&list_uids=168827350&dopt=GenBank&RID=WURX8KSX014&log$=nucltop&blast_rank=5) | Influenza A virus (A/Georgia/20/2006(H1N1)) segment 6 neuraminidase (NA) gene, complete cds | 26.3 (http://www.ncbi.nlm.nih.gov/blast/Blast.cgi#168827350) | 26.3 | 100% | 571 | 100% | |
| EU516198.1 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=Nucleotide&list_uids=168827348&dopt=GenBank&RID=WURX8KSX014&log$=nucltop&blast_rank=6) | Influenza A virus (A/Georgia/20/2006(H1N1)) segment 6 neuraminidase (NA) gene, partial cds | 26.3 (http://www.ncbi.nlm.nih.gov/blast/Blast.cgi#168827348) | 26.3 | 100% | 571 | 100% | |
| EU516197.1 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=Nucleotide&list_uids=168827346&dopt=GenBank&RID=WURX8KSX014&log$=nucltop&blast_rank=7) | Influenza A virus (A/Georgia/20/2006(H1N1)) segment 6 neuraminidase (NA) gene, complete cds | 26.3 (http://www.ncbi.nlm.nih.gov/blast/Blast.cgi#168827346) | 26.3 | 100% | 571 | 100% | |
| EU516196.1 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=Nucleotide&list_uids=168827344&dopt=GenBank&RID=WURX8KSX014&log$=nucltop&blast_rank=8) | Influenza A virus (A/Arizona/03/2007(H1N1)) segment 6 neuraminidase (NA) gene, complete cds | 26.3 (http://www.ncbi.nlm.nih.gov/blast/Blast.cgi#168827344) | 26.3 | 100% | 571 | 100% | |
| 26.3 (http://www.ncbi.nlm.nih.gov/blast/Blast.cgi#168825335) | 26.3 | 100% | 571 | 100% | |||
| EU516148.1 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=Nucleotide&list_uids=168825297&dopt=GenBank&RID=WURX8KSX014&log$=nucltop&blast_rank=10) | Influenza A virus (A/New Jersey/15/2007(H1N1)) segment 6 neuraminidase (NA) gene, complete cds | 26.3 (http://www.ncbi.nlm.nih.gov/blast/Blast.cgi#168825297) | 26.3 | 100% | 571 | 100% | |
| EU516141.1 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=Nucleotide&list_uids=168825289&dopt=GenBank&RID=WURX8KSX014&log$=nucltop&blast_rank=11) | Influenza A virus (A/Minnesota/23/2007(H1N1)) segment 6 neuraminidase (NA) gene, complete cds | 26.3 (http://www.ncbi.nlm.nih.gov/blast/Blast.cgi#168825289) | 26.3 | 100% | 571 | 100% | |
| EU516125.1 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=Nucleotide&list_uids=168825257&dopt=GenBank&RID=WURX8KSX014&log$=nucltop&blast_rank=12) | Influenza A virus (A/Hawaii/28/2007(H1N1)) segment 6 neuraminidase (NA) gene, complete cds | 26.3 (http://www.ncbi.nlm.nih.gov/blast/Blast.cgi#168825257) | 26.3 | 100% | 571 | 100% | |
| EU516123.1 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=Nucleotide&list_uids=168825253&dopt=GenBank&RID=WURX8KSX014&log$=nucltop&blast_rank=13) | Influenza A virus (A/Hawaii/28/2007(H1N1)) segment 6 neuraminidase (NA) gene, complete cds | 26.3 (http://www.ncbi.nlm.nih.gov/blast/Blast.cgi#168825253) | 26.3 | 100% | 571 | 100% | |
| EU516112.1 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=Nucleotide&list_uids=168825231&dopt=GenBank&RID=WURX8KSX014&log$=nucltop&blast_rank=14) | Influenza A virus (A/Hawaii/21/2007(H1N1)) segment 6 neuraminidase (NA) gene, complete cds | 26.3 (http://www.ncbi.nlm.nih.gov/blast/Blast.cgi#168825231) | 26.3 | 100% | 571 | 100% | |
| EU516028.1 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=Nucleotide&list_uids=168825205&dopt=GenBank&RID=WURX8KSX014&log$=nucltop&blast_rank=15) | Influenza A virus (A/Massachusetts/05/2007(H1N1)) segment 6 neuraminidase (NA) gene, complete cds | 26.3 (http://www.ncbi.nlm.nih.gov/blast/Blast.cgi#168825205) | 26.3 | 100% | 571 | 100% | |
| EU516027.1 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=Nucleotide&list_uids=168825203&dopt=GenBank&RID=WURX8KSX014&log$=nucltop&blast_rank=16) | Influenza A virus (A/Texas/31/2007(H1N1)) segment 6 neuraminidase (NA) gene, complete cds | 26.3 (http://www.ncbi.nlm.nih.gov/blast/Blast.cgi#168825203) | 26.3 | 100% |
http://www.recombinomics.com/News/03040803/H1N1_Tamiflu_US_Early.htmlCommentary (http://www.recombinomics.com/News/03040803/H1N1_Tamiflu_US_Early.html[/quote]Commentary) [/URL] [URL="http://www.newsnow.co.uk/nn/Recombinomics"] (http://www.recombinomics.com/feed.xml)
Early H1N1 Tamiflu Resistance in the United States
Recombinomics Commentary 15:43
March 4, 2008
The sudden appearance (http://www.recombinomics.com/News/01300804/H1N1_H274Y_H5N1.html) of Tamiflu (oseltamivir) resistance in H1N1 has “startled” influenza “experts”, as noted earlier. Analysis of H1N1 public sequences at Los Alamos indicated that H274Y began appearing in the United States in 2007 (http://www.recombinomics.com/News/01290802/H1N1_Tamiflu_US.html). However, closure of the Los Alamos data to the public has lead to movement of many of the sequences from Los Alamos to Genbank. Out of almost 1500 H1N1 human sequences at Genbank, six had H274Y (two were from the same patient).
The recent movement of sequences from Los Alamos was accompanied by newly released sequences, so the number of H1N1 sequences with H274Y has grown to 14 (from 11 patients), and like the sequences at Los Alamos, represent both H1N1 strains in circulation (http://www.recombinomics.com/News/02150801/H274Y_Concurrent.html), New Caledonia/20/1999 and Solomon Island/3/2006 (which has largely been replaced by Brisbance/59/2007). The new sequences move the first appearance back to 2006 in Georgia and raise the number of New Caledonia sequences with H274Y to seven (from five patients). The number of sequences with H274Y has grown to seven (from six patients), and expanded the number of states from one (Hawaii), to four (Arizona, Illinois, New Jersey).
The presence of the same change on two different genetic H1N1 backgrounds in addition to H5N1 genetic backgrounds decreases the likelihood that the acquisitions are linked to unrelated independent events, and moves the sudden appearance of Tamiflu resistance closer to the broader application of Tamiflu blankets to treat H5N1.
New Caledonia-like sequences
Georgia/20 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=Nucleotide&list_uids=168827350&dopt=GenBank&RID=WURX8KSX014&log$=nucltop&blast_rank=5)/2006
Kansas/UR06-0104 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=Nucleotide&list_uids=158454260&dopt=GenBank&RID=WUT14EXS016&log$=nucltop&blast_rank=1)/2007
Massachusetts/05 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=Nucleotide&list_uids=168825205&dopt=GenBank&RID=WURX8KSX014&log$=nucltop&blast_rank=15)/2007
Minnesota/23 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=Nucleotide&list_uids=168825289&dopt=GenBank&RID=WURX8KSX014&log$=nucltop&blast_rank=11)/2007
Texas/31 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=Nucleotide&list_uids=168825203&dopt=GenBank&RID=WURX8KSX014&log$=nucltop&blast_rank=16)/2007
Solomon Island (Brisbane/59)-like sequences
Arizona/03 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=Nucleotide&list_uids=168827344&dopt=GenBank&RID=WURX8KSX014&log$=nucltop&blast_rank=8)/2007
Illinois/10 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=Nucleotide&list_uids=168827352&dopt=GenBank&RID=WURX8KSX014&log$=nucltop&blast_rank=4)/2007
New Jersey/15 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=Nucleotide&list_uids=168825297&dopt=GenBank&RID=WURX8KSX014&log$=nucltop&blast_rank=10)/2007
New Jersey/16 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=Nucleotide&list_uids=168827354&dopt=GenBank&RID=WURX8KSX014&log$=nucltop&blast_rank=3)/2007
Hawaii/21 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=Nucleotide&list_uids=168825231&dopt=GenBank&RID=WURX8KSX014&log$=nucltop&blast_rank=14)/2007
Hawaii/28 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=Nucleotide&list_uids=168825257&dopt=GenBank&RID=WURX8KSX014&log$=nucltop&blast_rank=12)/2007
.
Influenza A virus (A/Indiana/01/2008(H1N1))
http://www.recombinomics.com/News/03220801/H274Y_US_Independent.html
>
>Tamiflu Resistance Challenges Influenza Genetics Dogma
>
>Recombinomics Commentary 01:49
>March 23, 2008
>
>The recently released sequences from H1N1 seasonal flu isolates in the
>United States by the Centers for Disease Control (CDC) further challenge
>the influenza genetics dogma, which maintains that such evolution is
>driven by selection of random mutations. Conceptually, such selection is
>easily understood when the virus is under attack by antivirals, such as
>oseltamivir (Tamiflu). Virus which randomly created the mutation which
>codes for H724Y would be about 1000 fold more efficient at budding from an
>infected cell, and therefore would have a strong selection advantage.
>
>However, the sudden apperance of the resistance was in countries which
>usually did not use Tamiflu, in patients who had not been treated with
>Tamiflu eliminates the antiviralo selection.
not yet. The selection could have happened in small settings
and then amplified by superspreaders.
We see it with the vaccine-mismatches, that the prevalence of certain
strains is hard to predict.
>Prior studies had indicated
>that H274Y would make the virus less fit, so the selective advantage in
>Tamiflu treated patients would not exist in influenza infected patients
>who were not under treatment, but the levels H274Y in almost 70% of H1N1
>in Norway clearly indicated that H1N1 with H274Y was evolutionarily fit.
yes, the "less fit" was maybe only valid in a certain genetical background,
but together with H274Y there were presumably other mutations which
already changed the virus, so that the old test-results no longer apply.
>This fitness was supported by the recently released sequences by the CDC.
>All were the Brisbayne/59 strain and mapped to the same branch of an H1N1
>phylogenetic tree (for both NA and HA) and in many cases the NA `sequences
>were identical, indicating the resistant strain could spread across the
>country (multiple sequences were released from Arizona in the west and New
>Jersey in the east).
>
>However, other isolates with H274Y mapped to another branch composed of
>isolates from western states (Hawaii and California), while other
>resistant strains were the genetically distinct New Caledonia strain,
>which was more prevalent in prior years. Thus, not only was the resistant
>H1N1 evolutionarily fit, but it was formed via multiple independent
>introductions (at least three in the small number of positives from the
>US).
this will become clearer when new sequences are being released.
If the trend is confirmed, that would indicate, that indeed
Tamiflu-evasion drove the evolution of H1N1.
>Moreover, like the isolates in Europe, the increase in resistance was
>sudden.
well, one year. Remember, we went from 11% Amantadine-resistance to
95% in one year.
It is mostly unknown what happens with the virus in Summer
in China and other (sub)-tropes.
>Some isolates were identified last season, but the vast majority
>was from this season, which is also true for countries in Europe, which
>began to report the detection when multiple isolates from Norway were
>resistant.
>
>The above scenario is difficult to explain by random mutations, even if a
>“fitness” mutation was widespread and help the resistant strains compete,
>because the sudden appearance does not correlate with countries that
>commonly use Tamiflu or recently increased the use of Tamiflu.
countries like Norway have no flu in summer. The virus is probably
newly introduced each year from the tropes.
>However, the change in Tamiflu usage preceding the sudden increase in
>H274Y in seasonal flu is found in the increased use of Tamiflu to treat
>H5N1.
but usage of Tamiflu for H5N1 is rare as compared with H1N1
>Although Tamiflu can inhibit the neuraminidase in all nine
>serotypes, it is less effective in N1.
hmm, I didn't know. Seemed to work rather well for H1N1 before.
> Moreover, it is less effective in H5N1 than H1N1,
presumably depends on the strain/clade
>and in Tamiflu blanket applications, it is used at half
>the treatment dosage. This set of circumstances lead to the report of
>Tamiflu resistance Vietnam in 2005 and the genetic change in H5N1 was
>identical to the change in H1N1.
but it did not spread to other humans
>Moreover, the Tamiflu resistance in Vietnam was also associated with a
>reduced case fatality rate in northern Vietnam in 2005. In the north, the
>fatality rate fell from 70% in 2004, to less than 10% in 2005. Moreover,
>the lower case fatality rate was coincident with more efficient
>transmission to humans, increasing the likelihood of co-infections of H5N1
>and H1N1, including H5N1 with H274Y linked to Tamiflu blanket
>applications.
no such case had been reported yet
>Although clusters in northern Vietnam were larger, the
>efficiency of transmission human to human was still markedly below
>seasonal flu, but recombination in co-infected host would allow for the
>acquisition of H274Y by H1N1, which could then be more efficiently spread
>human to human.
why just recombine exactly this single H274Y and no other positions ?
The virus doesn't know in advance.
>In addition, H274Y could be acquired by additional H1 serotypes in birds
>and swine followed by acquisition of H1N1 at distant locations, such as
>Norway.
birds and swine rarely get or transmit human H1N1
> In either case, the introduction of H274Y into the human
>population could then be followed by acquisition of H274Y by other strains
>via recombination, and would not require new selection of random
>mutations.
then we should see "these acquisitions" more often, not just with
H274Y.
>Moreover, the sudden appearance of H274Y in human populations would follow
>the sudden increase in Tamiflu treatment of H5N1 in multiple locations,
>including Vietnam, Indonesia, Turkey, and Egypt.
as well as the sudden increase in Tamiflu treatment of H3N2,H1N1
in even more locations
I'd like to see a list of Tamiflu usage by country and year.
Also for Amantadine 2003-2006.
1) Solomon
2) Caledonia
3) Brisbane
can we make a first list of % resistant as function of group and country ?
Seems that the sequences are coming in now ...
Hopefully some European countries will join (Denmark ?)
No, the segregation in the US can be further defined through phylogentic analysis. The earlier introductions (late 2006 and early 2007) are New Caledonia. This season, all public sequences are Brisbane, but they represent two more intoductions. One introdution is in a "western" branch composed of Hawaii and California (and includes two positives in Hawaii). The second branch is more widespread and includes multiple isolates in Arizona and New Jersey.
The story is in the sequence, and the H274Y is NOT due to random mutation. Recombination remains the name of the game.
http://www.recombinomics.com/News/03220801/H274Y_US_Independent.htmlCommentary (http://www.recombinomics.com/feed.xml) [/URL]
Independent Acquistions of Tamiflu Resistance in the US
Recombinomics Commentary 13:11
March 22, 2008
The US Center for Disease Control (CDC) has released addition H1N1 sequences, including those from 2008 isolates. These data include additional NA sequences with H274Y (see list [URL="http://www.flutrackers.com/forum/showthread.php?t=58160"]here (http://www.newsnow.co.uk/nn/Recombinomics)). The new data supports multiple introductions of H274Y, which creates significant problems for current influenza genetics dogma, which maintains that such changes are due to selection of random mutations.
The problem of Tamiflu resistance has become increasingly clear. It achieved widespread notice when countries in Europe began reporting the resistance. All of the resistance was in H1N1 seasonal flu, but the sudden appearance (http://www.recombinomics.com/News/01300804/H1N1_H274Y_H5N1.html) was not linked (http://www.recombinomics.com/News/02150801/H274Y_Concurrent.html) to Tamiflu usage. The highest frequency was initially reported in Norway, and the high frequency has been maintained. In the latest report (http://www.who.int/csr/disease/influenza/resistanceweb20080320.pdf), 127 of 184 H1N1 isolates (69%) are H274Y positive. Similarly, 106 of 279 H1N1 isolates (38%) in France have H274Y. In contrast, in countries such as Japan, which have higher frequencies of Tamiflu usage, the frequency is only 5%. In the United States (http://www.recombinomics.com/News/01290802/H1N1_Tamiflu_US.html), the frequency in the latest CDC weekly report (http://www.cdc.gov/flu/weekly/fluactivity.htm) is 9.1% (59 of 646 H1N1 isolates).
In the United States, the earlier resistance (2006/2007 season) was exclusively in the New Caledonia strain. This season, all of the recently released positives are in the Brisbane/59 strain. However, these new isolates represent two independent acquisitions. One branch of the phylogenetic tree is composed of isolates from Hawaii and California, Two of the isolates on this branch have H274Y and both are from Hawaii. These data represent a recent acquisition because H274Y is only in a subset of the isolates. A separate branch is more widespread in the US. The two states with the most positives on this branch are Arizona and New Jersey (see list below).
The presence of H274Y on multiple branches of phylogenetic trees of H1N1 isolates raises serious questions about current dogma on influenza genetics. Continued selection of H274Y is not consistent with Tamiflu usage or the branch clustering, which is highlighted by the phylogenetic analysis and the sudden appearance of the resistance in the US or other countries, especially Norway and France where the frequency of H274Y is alarmingly high.
New Caledonia-like sequences
Georgia/20 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=Nucleotide&list_uids=168827350&dopt=GenBank&RID=WURX8KSX014&log$=nucltop&blast_rank=5)/2006
Kansas/UR06-0104 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=Nucleotide&list_uids=158454260&dopt=GenBank&RID=WUT14EXS016&log$=nucltop&blast_rank=1)/2007
Massachusetts/05 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=Nucleotide&list_uids=168825205&dopt=GenBank&RID=WURX8KSX014&log$=nucltop&blast_rank=15)/2007
Minnesota/23 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=Nucleotide&list_uids=168825289&dopt=GenBank&RID=WURX8KSX014&log$=nucltop&blast_rank=11)/2007
Texas/31 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=Nucleotide&list_uids=168825203&dopt=GenBank&RID=WURX8KSX014&log$=nucltop&blast_rank=16)/2007
Brisbane/59-like sequences
Mainland branch
Arizona/03 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=Nucleotide&list_uids=168827344&dopt=GenBank&RID=WURX8KSX014&log$=nucltop&blast_rank=8)/2007
Arizona/13 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=Nucleotide&list_uids=170181774&dopt=GenBank&RID=Y9YVPNPV016&log$=nucltop&blast_rank=2)/2007
Arizona/14 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=Nucleotide&list_uids=170181768&dopt=GenBank&RID=Y9YVPNPV016&log$=nucltop&blast_rank=3)/2007
Arizona/15 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=Nucleotide&list_uids=170181692&dopt=GenBank&RID=Y9YVPNPV016&log$=nucltop&blast_rank=9)/2007
Illinois/10 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=Nucleotide&list_uids=168827352&dopt=GenBank&RID=WURX8KSX014&log$=nucltop&blast_rank=4)/2007
Indiana/01 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=Nucleotide&list_uids=170181778&dopt=GenBank&RID=Y9YVPNPV016&log$=nucltop&blast_rank=19)/2008
Maryland/04 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=Nucleotide&list_uids=170181752&dopt=GenBank&RID=Y9YVPNPV016&log$=nucltop&blast_rank=5)/2007
New Jersey/06 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=Nucleotide&list_uids=170181784&dopt=GenBank&RID=Y9YVPNPV016&log$=nucltop&blast_rank=1)/2007
New Jersey/15 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=Nucleotide&list_uids=168825297&dopt=GenBank&RID=WURX8KSX014&log$=nucltop&blast_rank=10)/2007
New Jersey/16 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=Nucleotide&list_uids=168827354&dopt=GenBank&RID=WURX8KSX014&log$=nucltop&blast_rank=3)/2007
Pennsylvania/02 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=Nucleotide&list_uids=170181710&dopt=GenBank&RID=Y9YVPNPV016&log$=nucltop&blast_rank=8)/2008
New Jersey/20 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=Nucleotide&list_uids=170181730&dopt=GenBank&RID=Y9YVPNPV016&log$=nucltop&blast_rank=6)/2007
New Jersey/05 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=Nucleotide&list_uids=170181722&dopt=GenBank&RID=Y9YVPNPV016&log$=nucltop&blast_rank=7)/2008
Wisconsin/01 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=Nucleotide&list_uids=170181754&dopt=GenBank&RID=Y9YVPNPV016&log$=nucltop&blast_rank=4)/2008
"Western" branch
Hawaii/21 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=Nucleotide&list_uids=168825231&dopt=GenBank&RID=WURX8KSX014&log$=nucltop&blast_rank=14)/2007
Hawaii/28 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=Nucleotide&list_uids=168825257&dopt=GenBank&RID=WURX8KSX014&log$=nucltop&blast_rank=12)/2007
.
1) Solomon
2) Caledonia
3) Brisbane
can we make a first list of % resistant as function of group and country ?
Seems that the sequences are coming in now ...
Hopefully some European countries will join (Denmark ?)
http://www.recombinomics.com/News/03230801/H274Y_Dogma.html
http://www.recombinomics.com/News/03040803/H1N1_Tamiflu_US_Early.html
>
>In addition, H274Y could be acquired by additional H1 serotypes in birds
>and swine followed by acquisition of H1N1 at distant locations, such as
>Norway.
birds and swine rarely get or transmit human H1N1
Actually, the above should say N1. N1 polymorphisms go to birds, humans, and swine as seen in travel log below
gbDQ493078.1 Influenza A virus (A/Vietnam/CL2009/2005(H5N1)... 28.2 0.55
gbDQ250165.1 Influenza A virus (A/Vietnam/CL2009/2005(H5N1)... 28.2 0.55
gbCY030737.1 Influenza A virus (A/swine/Tennessee/9/1978(H1... 26.3 2.2
gbCY029393.1 Influenza A virus (A/chicken/Yunnan/1252/2003(... 26.3 2.2
gbCY029386.1 Influenza A virus (A/chicken/Yunnan/1251/2003(... 26.3 2.2
gbCY029379.1 Influenza A virus (A/chicken/Yunnan/1083/2003(... 26.3 2.2
gbCY029372.1 Influenza A virus (A/duck/Yunnan/662/2003(H5N1... 26.3 2.2
gbCY029365.1 Influenza A virus (A/chicken/Yunnan/564/2003(H... 26.3 2.2
gbCY029358.1 Influenza A virus (A/duck/Yunnan/215/2003(H5N1... 26.3 2.2
gbCY029351.1 Influenza A virus (A/duck/Yunnan/119/2003(H5N1... 26.3 2.2
gbCY029344.1 Influenza A virus (A/chicken/Yunnan/1215/2002(... 26.3 2.2
gbCY029260.1 Influenza A virus (A/silky chicken/Shantou/475... 26.3 2.2
gbCY029246.1 Influenza A virus (A/chicken/Shantou/3744/2003... 26.3 2.2
gbEU502888.1 Influenza A virus (A/swine/Shanghai/1/2005(H1N... 26.3 2.2
gbEU429785.1 Influenza A virus (A/duck/Eastern China/89/200... 26.3 2.2
gbEU429779.1 Influenza A virus (A/duck/Eastern China/48/200... 26.3 2.2
gbEU429778.1 Influenza A virus (A/duck/Eastern China/37/200... 26.3 2.2
gbEU429765.1 Influenza A virus (A/duck/Eastern China/89/200... 26.3 2.2
gbEU429764.1 Influenza A virus (A/duck/Eastern China/58/200... 26.3 2.2
gbEU429763.1 Influenza A virus (A/duck/Eastern China/51/200... 26.3 2.2
gbEU429759.1 Influenza A virus (A/duck/Eastern China/59/200... 26.3 2.2
gbEU429758.1 Influenza A virus (A/duck/Eastern China/54/200... 26.3 2.2
gbEU429757.1 Influenza A virus (A/duck/Eastern China/40/200... 26.3 2.2
gbEU429747.1 Influenza A virus (A/duck/Eastern China/304/20... 26.3 2.2
gbEU417843.1 Influenza A virus (A/swine/Finistere/2899/1982... 26.3 2.2
gbCY029939.1 Influenza A virus (A/chicken/Vietnam/15/2004(H... 26.3 2.2
gbCY029777.1 Influenza A virus (A/chicken/Malaysia/5223/200... 26.3 2.2
gbCY028782.1 Influenza A virus (A/swine/California/T9001707... 26.3 2.2
gbCY028790.1 Influenza A virus (A/swine/Iowa/1/1986(H1N1)) ... 26.3 2.2
gbCY028718.1 Influenza A virus (A/chicken/Vietnam/24/2004(H... 26.3 2.2
gbCY028710.1 Influenza A virus (A/chicken/Vietnam/23/2004(H... 26.3 2.2
gbCY028702.1 Influenza A virus (A/chicken/Vietnam/10/2004(H... 26.3 2.2
gbCY028437.1 Influenza A virus (A/swine/Tennessee/7/1978(H1... 26.3 2.2
gbCY028429.1 Influenza A virus (A/swine/Tennessee/4/1978(H1... 26.3 2.2
gbEU294373.1 Influenza A virus (A/Viet Nam/HN31242/2007(H5N... 26.3 2.2
gbEU294372.1 Influenza A virus (A/Viet Nam/HN31242/2007(H5N... 26.3 2.2
gbEU329179.1 Influenza A virus (A/wild duck/Hunan/021/2005(... 26.3 2.2
gbEU221248.1 Influenza A virus (A/clouded leopard/Thailand/... 26.3 2.2
gbEF112344.1 Influenza A virus (A/open-billed stork/Nakhons... 26.3 2.2
gbEF112343.1 Influenza A virus (A/open-billed stork/Nakhons... 26.3 2.2
gbEF112342.1 Influenza A virus (A/open-billed stork/Nakhons... 26.3 2.2
gbEF112341.1 Influenza A virus (A/open-billed stork/Nakhons... 26.3 2.2
gbEF112340.1 Influenza A virus (A/open-billed stork/Nakhons... 26.3 2.2
gbEF112339.1 Influenza A virus (A/open-billed stork/Nakhons... 26.3 2.2
gbEF112338.1 Influenza A virus (A/open-billed stork/Nakhons... 26.3 2.2
gbEF112337.1 Influenza A virus (A/open-billed stork/Nakhons... 26.3 2.2
gbEF112336.1 Influenza A virus (A/open-billed stork/Nakhons... 26.3 2.2
gbEF112335.1 Influenza A virus (A/open-billed stork/Nakhons... 26.3 2.2
gbEF112334.1 Influenza A virus (A/open-billed stork/Nakhons... 26.3 2.2
gbEF112333.1 Influenza A virus (A/open-billed stork/Nakhons... 26.3 2.2
gbEF112332.1 Influenza A virus (A/open-billed stork/Nakhons... 26.3 2.2
gbEF112331.1 Influenza A virus (A/open-billed stork/Nakhons... 26.3 2.2
gbEF112330.1 Influenza A virus (A/open-billed stork/Nakhons... 26.3 2.2
gbEF112329.1 Influenza A virus (A/open-billed stork/Nakhons... 26.3 2.2
gbEF112328.1 Influenza A virus (A/open-billed stork/Nakhons... 26.3 2.2
gbEF112327.1 Influenza A virus (A/open-billed stork/Nakhons... 26.3 2.2
gbEF112326.1 Influenza A virus (A/open-billed stork/Nakhons... 26.3 2.2
gbEF112325.1 Influenza A virus (A/open-billed stork/Nakhons... 26.3 2.2
gbEF112324.1 Influenza A virus (A/open-billed stork/Nakhons... 26.3 2.2
gbEF112323.1 Influenza A virus (A/open-billed stork/Nakhons... 26.3 2.2
gbEF112322.1 Influenza A virus (A/open-billed stork/Nakhons... 26.3 2.2
gbEF112321.1 Influenza A virus (A/open-billed stork/Nakhons... 26.3 2.2
gbEF112320.1 Influenza A virus (A/open-billed stork/Nakhons... 26.3 2.2
gbEF112319.1 Influenza A virus (A/open-billed stork/Nakhons... 26.3 2.2
gbEF112318.1 Influenza A virus (A/open-billed stork/Bangkok... 26.3 2.2
gbEF112317.1 Influenza A virus (A/open-billed stork/Bangkok... 26.3 2.2
gbCY028189.1 Influenza A virus (A/swine/Wisconsin/30747/197... 26.3 2.2
gbCY028181.1 Influenza A virus (A/swine/Tennessee/3/1978(H1... 26.3 2.2
gbCY028173.1 Influenza A virus (A/swine/Iowa/2/1987(H1N1)) ... 26.3 2.2
gbEU233418.1 Influenza A virus (A/chicken/Thailand/ICRC-V14... 26.3 2.2
gbCY027509.1 Influenza A virus (A/swine/Iowa/2/1985(H1N1)) ... 26.3 2.2
gbCY027525.1 Influenza A virus (A/swine/Tennessee/8/1978(H1... 26.3 2.2
gbCY027517.1 Influenza A virus (A/swine/Tennessee/5/1978(H1... 26.3 2.2
gbEU186412.1 Influenza A virus (A/swine/Korea/GC0503/2005(H... 26.3 2.2
gbCY027157.1 Influenza A virus (A/swine/Iowa/24297/1991(H1N... 26.3 2.2
gbCY027309.1 Influenza A virus (A/swine/Tennessee/2/1978(H1... 26.3 2.2
gbCY027301.1 Influenza A virus (A/swine/Tennessee/118/1977(... 26.3 2.2
gbCY026493.1 Influenza A virus (A/swine/Tennessee/112/1977(... 26.3 2.2
gbCY026485.1 Influenza A virus (A/swine/Tennessee/106/1977(... 26.3 2.2
gbCY026477.1 Influenza A virus (A/swine/Tennessee/105/1977(... 26.3 2.2
gbCY026469.1 Influenza A virus (A/swine/Iowa/100/1977(H1N1)... 26.3 2.2
gbCY026461.1 Influenza A virus (A/swine/Tennessee/10/1976(H... 26.3 2.2
gbCY026453.1 Influenza A virus (A/swine/Ontario/6/1981(H1N1... 26.3 2.2
gbCY026445.1 Influenza A virus (A/swine/Ontario/3/1981(H1N1... 26.3 2.2
gbCY026437.1 Influenza A virus (A/swine/Ontario/2/1981(H1N1... 26.3 2.2
gbCY026421.1 Influenza A virus (A/swine/Tennessee/23/1976(H... 26.3 2.2
gbEU146623.1 Influenza A virus (A/Indonesia/5/2005(H5N1)) s... 26.3 2.2
gbCY026301.1 Influenza A virus (A/swine/Wisconsin/2/1966(H1... 26.3 2.2
gbCY026293.1 Influenza A virus (A/swine/Wisconsin/1/1967(H1... 26.3 2.2
gbCY026285.1 Influenza A virus (A/swine/Wisconsin/1/1957(H1... 26.3 2.2
gbDQ990005.1 Influenza A virus (A/open-billed stork/Nakhons... 26.3 2.2
gbDQ989997.1 Influenza A virus (A/open-billed stork/Nakhons... 26.3 2.2
gbDQ989989.1 Influenza A virus (A/open-billed stork/Nakhons... 26.3 2.2
gbDQ989981.1 Influenza A virus (A/open-billed stork/Suphanb... 26.3 2.2
gbDQ989971.1 Influenza A virus (A/open-billed stork/Nakhons... 26.3 2.2
gbDQ989963.1 Influenza A virus (A/open-billed stork/Nakhons... 26.3 2.2
gbCY026141.1 Influenza A virus (A/Wisconsin/301/1976(H1N1))... 26.3 2.2
gbEU139842.1 Influenza A virus (A/swine/Iowa/00239/2004(H1N... 26.3 2.2
gbEU139839.1 Influenza A virus (A/swine/North Carolina/3688... 26.3 2.2
gbEU139835.1 Influenza A virus (A/swine/Wisconsin/1/1968(H1... 26.3 2.2
gbCY025255.1 Influenza A virus (A/swine/Virginia/670/1987(H... 26.3 2.2
gbCY025207.1 Influenza A virus (A/swine/Tennessee/37/1977(H... 26.3 2.2
gbEU124219.1 Influenza A virus (A/Pigeon/Indonesia/Rohkit16... 26.3 2.2
gbEU124218.1 Influenza A virus (A/Chicken/Indonesia/Agam163... 26.3 2.2
gbEU124217.1 Influenza A virus (A/Chicken/Indonesia/Siak163... 26.3 2.2
gbEU124216.1 Influenza A virus (A/Chicken/Indonesia/Padang1... 26.3 2.2
gbEU124060.1 Influenza A virus (A/Chicken/Indonesia/Wates83... 26.3 2.2
gbEU124057.1 Influenza A virus (A/Chicken/Indonesia/Wates77... 26.3 2.2
gbEU128239.1 Influenza A virus (A/Anhui/1/2005(H5N1)) segme... 26.3 2.2
gbEU118144.1 Influenza A virus (A/chicken/Vietnam/TY25/2005... 26.3 2.2
gbEU118143.1 Influenza A virus (A/chicken/Vietnam/TY9/2005(... 26.3 2.2
gbEU118141.1 Influenza A virus (A/chicken/Vietnam/G04/2004(... 26.3 2.2
gbEU118140.1 Influenza A virus (A/duck/Vietnam/5082/2005(H5... 26.3 2.2
gbEU118139.1 Influenza A virus (A/duck/Vietnam/5004/2005(H5... 26.3 2.2
gbEU118137.1 Influenza A virus (A/duck/Vietnam/5001/2005(H5... 26.3 2.2
gbEU118127.1 Influenza A virus (A/chicken/Vietnam/TY31/2005... 26.3 2.2
gbCY025012.1 Influenza A virus (A/swine/Kansas/3024/1987(H1... 26.3 2.2
gbCY025059.1 Influenza A virus (A/swine/Tennessee/48/1977(H... 26.3 2.2
gbCY024927.1 Influenza A virus (A/Ohio/3559/1988(H1N1)) seg... 26.3 2.2
gbCY025004.1 Influenza A virus (A/swine/Arizona/148/1977(H1... 26.3 2.2
gbCY024996.1 Influenza A virus (A/swine/Wisconsin/663/1980(... 26.3 2.2
gbCY024988.1 Influenza A virus (A/swine/Tennessee/10/1978(H... 26.3 2.2
gbCY024980.1 Influenza A virus (A/swine/Tennessee/88/1977(H... 26.3 2.2
gbCY024972.1 Influenza A virus (A/swine/Tennessee/87/1977(H... 26.3 2.2
gbCY024964.1 Influenza A virus (A/swine/Tennessee/86/1977(H... 26.3 2.2
gbCY024956.1 Influenza A virus (A/swine/Tennessee/84/1977(H... 26.3 2.2
gbCY024952.1 Influenza A virus (A/swine/Tennessee/96/1977(H... 26.3 2.2
gbCY024944.1 Influenza A virus (A/swine/Tennessee/61/1977(H... 26.3 2.2
gbCY024935.1 Influenza A virus (A/swine/Minnesota/24/1975(H... 26.3 2.2
gbEF501996.1 Influenza A virus (A/duck/Phitsanulok/NIAH6-5-... 26.3 2.2
gbEF501995.1 Influenza A virus (A/chicken/Phichit/NIAH6-4-0... 26.3 2.2
gbDQ889687.1 Influenza A virus (A/Iowa/CEID23/2005(H1N1)) n... 26.3 2.2
gbEU045400.1 Influenza A virus (A/swine/Italy/37460/2007(H1... 26.3 2.2
gbEU045398.1 Influenza A virus (A/swine/Italy/1302/2006(H1N... 26.3 2.2
gbEU045397.1 Influenza A virus (A/swine/Italy/204931/2005(H... 26.3 2.2
gbEU045396.1 Influenza A virus (A/swine/Italy/125746/2005(H... 26.3 2.2
gbEU045395.1 Influenza A virus (A/swine/Italy/290851/2004(H... 26.3 2.2
gbEU045394.1 Influenza A virus (A/swine/Italy/258654/2004(H... 26.3 2.2
gbEU045393.1 Influenza A virus (A/swine/Italy/247578/2004(H... 26.3 2.2
gbEU045392.1 Influenza A virus (A/swine/Italy/112147/2004(H... 26.3 2.2
gbEU045391.1 Influenza A virus (A/swine/Italy/90315/2004(H1... 26.3 2.2
gbEU045390.1 Influenza A virus (A/swine/Italy/77048/2004(H1... 26.3 2.2
gbEU045389.1 Influenza A virus (A/swine/Italy/65296/2004(H1... 26.3 2.2
gbEU045388.1 Influenza A virus (A/swine/Italy/53949/2004(H1... 26.3 2.2
gbEU045386.1 Influenza A virus (A/swine/Italy/207828/2002(H... 26.3 2.2
gbEU045385.1 Influenza A virus (A/swine/Italy/110093/2002(H... 26.3 2.2
gbEU045384.1 Influenza A virus (A/swine/Italy/4230/2002(H1N... 26.3 2.2
gbEU045383.1 Influenza A virus (A/swine/Italy/10169/2001(H1... 26.3 2.2
gbEU045382.1 Influenza A virus (A/swine/Italy/5433/2001(H1N... 26.3 2.2
gbEU045381.1 Influenza A virus (A/swine/Italy/4443/2000(H1N... 26.3 2.2
gbCY022972.1 Influenza A virus (A/swine/Iowa/31483/1988(H1N... 26.3 2.2
gbCY022964.1 Influenza A virus (A/swine/Iowa/1/1987(H1N1)) ... 26.3 2.2
gbCY022996.1 Influenza A virus (A/swine/Wisconsin/629/1980(... 26.3 2.2
gbCY022988.1 Influenza A virus (A/swine/Virginia/671/1987(H... 26.3 2.2
gbCY022980.1 Influenza A virus (A/swine/Ontario/1/1981(H1N1... 26.3 2.2
gbCY022956.1 Influenza A virus (A/swine/Iowa/1/1977(H1N1)) ... 26.3 2.2
gbEF178533.1 Influenza A virus (A/tiger/Thailand/VSMU-23-CB... 26.3 2.2
gbEF178530.1 Influenza A virus (A/tiger/Thailand/VSMU-11-SP... 26.3 2.2
gbEF178529.1 Influenza A virus (A/brown-headed gull/Thailan... 26.3 2.2
gbEF178519.1 Influenza A virus (A/golden pheasant/Thailand/... 26.3 2.2
gbEF178507.1 Influenza A virus (A/tree sparrow/Thailand/VSM... 26.3 2.2
gbCY022319.1 Influenza A virus (A/swine/Iowa/1/1985(H1N1)) ... 26.3 2.2
gbCY022327.1 Influenza A virus (A/swine/Iowa/3/1985(H1N1)) ... 26.3 2.2
gbCY022335.1 Influenza A virus (A/swine/Iowa/17672/1988(H1N... 26.3 2.2
gbCY022431.1 Influenza A virus (A/swine/Wisconsin/1915/1988... 26.3 2.2
gbCY022471.1 Influenza A virus (A/swine/Kansas/3228/1987(H1... 26.3 2.2
gbCY022479.1 Influenza A virus (A/swine/Maryland/23239/1991... 26.3 2.2
gbCY022463.1 Influenza A virus (A/swine/Wisconsin/8/1980(H1... 26.3 2.2
gbCY022455.1 Influenza A virus (A/swine/Wisconsin/661/1980(... 26.3 2.2
gbCY022447.1 Influenza A virus (A/swine/Wisconsin/641/1980(... 26.3 2.2
gbCY022439.1 Influenza A virus (A/swine/Wisconsin/2/1970(H1... 26.3 2.2
gbCY022423.1 Influenza A virus (A/swine/Wisconsin/11/1980(H... 26.3 2.2
gbCY022415.1 Influenza A virus (A/swine/Wisconsin/1/1971(H1... 26.3 2.2
gbCY022407.1 Influenza A virus (A/swine/Tennessee/11/1978(H... 26.3 2.2
gbCY022391.1 Influenza A virus (A/swine/Ontario/7/1981(H1N1... 26.3 2.2
gbCY022383.1 Influenza A virus (A/swine/Ontario/4/1981(H1N1... 26.3 2.2
gbCY022375.1 Influenza A virus (A/swine/Nebraska/123/1977(H... 26.3 2.2
gbCY022367.1 Influenza A virus (A/swine/Minnesota/5892-7/19... 26.3 2.2
gbCY022359.1 Influenza A virus (A/swine/Minnesota/27/1976(H... 26.3 2.2
gbCY022351.1 Influenza A virus (A/swine/Kentucky/1/1976(H1N... 26.3 2.2
gbCY022303.1 Influenza A virus (A/swine/Tennessee/82/1977(H... 26.3 2.2
gbCY022295.1 Influenza A virus (A/swine/Tennessee/79/1977(H... 26.3 2.2
gbCY022287.1 Influenza A virus (A/swine/Tennessee/65/1977(H... 26.3 2.2
gbCY022279.1 Influenza A virus (A/swine/Tennessee/62/1977(H... 26.3 2.2
gbCY022271.1 Influenza A virus (A/swine/Tennessee/10/1977(H... 26.3 2.2
gbEF670480.1 Influenza A virus (A/duck/Hunan/15/2004(H5N1))... 26.3 2.2
gbCY022143.1 Influenza A virus (A/swine/Tennessee/64/1977(H... 26.3 2.2
gbCY022135.1 Influenza A virus (A/swine/Tennessee/49/1977(H... 26.3 2.2
gbCY022127.1 Influenza A virus (A/swine/Tennessee/31/1977(H... 26.3 2.2
gbCY022119.1 Influenza A virus (A/swine/Tennessee/21/1977(H... 26.3 2.2
gbCY022111.1 Influenza A virus (A/swine/Tennessee/19/1977(H... 26.3 2.2
gbCY022103.1 Influenza A virus (A/swine/Iowa/4/1976(H1N1)) ... 26.3 2.2
gbEF593104.1 Influenza A virus (A/chicken/Thailand/vsmu-3-B... 26.3 2.2
gbCY022063.1 Influenza A virus (A/swine/Tennessee/19/1976(H... 26.3 2.2
gbCY022071.1 Influenza A virus (A/swine/Iowa/1/1976(H1N1)) ... 26.3 2.2
gbCY022055.1 Influenza A virus (A/swine/Tennessee/17/1976(H... 26.3 2.2
gbCY022047.1 Influenza A virus (A/swine/Tennessee/15/1976(H... 26.3 2.2
gbCY022039.1 Influenza A virus (A/swine/Tennessee/7/1976(H1... 26.3 2.2
gbCY022031.1 Influenza A virus (A/swine/Tennessee/3/1976(H1... 26.3 2.2
gbCY021959.1 Influenza A virus (A/New Jersey/1976(H1N1)) se... 26.3 2.2
gbEF566216.1 Influenza A virus (A/Duck/Viet Nam/367/2005(H5... 26.3 2.2
gbEF566214.1 Influenza A virus (A/Chicken/Viet Nam/NCVD12/2... 26.3 2.2
gbEF566211.1 Influenza A virus (A/Duck/Viet Nam/NCVD04/2005... 26.3 2.2
gbEF566210.1 Influenza A virus (A/Duck/Viet Nam/NCVD03/2005... 26.3 2.2
gbEF566209.1 Influenza A virus (A/Muscovy Duck/Viet Nam/NCV... 26.3 2.2
gbEF566208.1 Influenza A virus (A/Duck/Viet Nam/NCVD01/2005... 26.3 2.2
gbEF566207.1 Influenza A virus (A/Duck/Viet Nam/NCVD08/2005... 26.3 2.2
gbEF566206.1 Influenza A virus (A/Duck/Viet Nam/NCVD07/2005... 26.3 2.2
gbEF566205.1 Influenza A virus (A/Duck/Viet Nam/NCVD05/2005... 26.3 2.2
gbDQ520854.1 Influenza A virus (A/duck/Hubei/3/2005(H5N1)) ... 26.3 2.2
gbDQ520853.1 Influenza A virus (A/chicken/Zhejiang/24/2005(... 26.3 2.2
gbEF190984.1 Influenza A virus (A/lvPR8/34(H1N1)) segment 6... 26.3 2.2
gbEF190976.1 Influenza A virus (A/hvPR8/34(H1N1)) segment 6... 26.3 2.2
gbEF541395.1 Influenza A virus (A/Indonesia/5/05(H5N1)) seg... 26.3 2.2
gbEF541476.1 Influenza A virus (A/chicken/Laos/7191/2004(H5... 26.3 2.2
gbEF541475.1 Influenza A virus (A/chicken/Viet Nam/1/2004(H... 26.3 2.2
gbEF541473.1 Influenza A virus (A/Thailand/Chaiyaphum/622/2... 26.3 2.2
gbEF541472.1 Influenza A virus (A/Thailand/SP83/2004(H5N1))... 26.3 2.2
gbEF541471.1 Influenza A virus (A/Thailand/Kan353/2004(H5N1... 26.3 2.2
gbEF541470.1 Influenza A virus (A/Thailand/16/2004(H5N1)) s... 26.3 2.2
gbEF541467.1 Influenza A virus (A/Viet Nam/1203/2004(H5N1))... 26.3 2.2
gbEF541466.1 Influenza A virus (A/Viet Nam/1194/2004(H5N1))... 26.3 2.2
gbEF541464.1 Influenza A virus (A/chicken/Korea/es/2003(H5N... 26.3 2.2
gbCY021605.1 Influenza A virus (A/mallard/Ohio/184/1986(Mix... 26.3 2.2
gbEF512562.1 Influenza A virus (A/Prachinburi/6231/2004(H5N... 26.3 2.2
gbCY021431.1 Influenza A virus (A/mallard/Ohio/181/1986(H3N... 26.3 2.2
gbCY020463.1 Influenza A virus (A/Iowa/1943(H1N1)) segment ... 26.3 2.2
gbCY020287.1 Influenza A virus (A/AA/Marton/1943(H1N1)) seg... 26.3 2.2
gbEF473078.1 Influenza A virus (A/chicken/Cambodia/022LC3b/... 26.3 2.2
gbEF473077.1 Influenza A virus (A/chicken/Cambodia/022LC2b/... 26.3 2.2
gbEF473076.1 Influenza A virus (A/chicken/Cambodia/013LC1b/... 26.3 2.2
gbEF473071.1 Influenza A virus (A/goose/Cambodia/28/2004(H5... 26.3 2.2
gbEF473067.1 Influenza A virus (A/goose/Cambodia/022b/2005(... 26.3 2.2
gbEF467823.1 Influenza A virus (A/Puerto Rico/8/34(H1N1)) s... 26.3 2.2
gbEF467801.1 Influenza A virus (A/chicken/Thailand/2/04(H5N... 26.3 2.2
gbAY553832.2 Influenza A virus (A/little grebe/Thailand/Phi... 26.3 2.2
gbEF456804.1 Influenza A virus (A/Viet Nam/HN30408/2005(H5N... 26.3 2.2
gbEF456801.1 Influenza A virus (A/Viet Nam/JP14/2005(H5N1))... 26.3 2.2
gbEF456800.1 Influenza A virus (A/Viet Nam/JP4207/2005(H5N1... 26.3 2.2
gbEF456796.1 Influenza A virus (A/Viet Nam/JP178/2004(H5N1)... 26.3 2.2
gbEF456793.1 Influenza A virus (A/Cambodia/JP52a/2005(H5N1)... 26.3 2.2
gbCY019957.1 Influenza A virus (A/Alaska/1935(H1N1)) segmen... 26.3 2.2
gbDQ835315.1 Influenza A virus (A/China/GD01/2006(H5N1)) se... 26.3 2.2
gbEF124796.1 Influenza A virus (A/Owston's civet/Vietnam/1/... 26.3 2.2
gbAY834280.2 Influenza A virus (A/Tiger/Thailand/VSMU-1-SPB... 26.3 2.2
gbEF124340.1 Influenza A virus (A/chicken/Fujian/12239/2005... 26.3 2.2
gbEF124339.1 Influenza A virus (A/duck/Guangxi/2143/2006(H5... 26.3 2.2
gbEF124338.1 Influenza A virus (A/chicken/Guangxi/1951/2006... 26.3 2.2
gbEF124337.1 Influenza A virus (A/goose/Guangxi/1898/2006(H... 26.3 2.2
gbEF124336.1 Influenza A virus (A/duck/Guangxi/1830/2006(H5... 26.3 2.2
gbEF124335.1 Influenza A virus (A/goose/Guangxi/1633/2006(H... 26.3 2.2
gbEF124334.1 Influenza A virus (A/duck/Guangxi/1550/2006(H5... 26.3 2.2
gbEF124333.1 Influenza A virus (A/goose/Guangxi/1458/2006(H... 26.3 2.2
gbEF124332.1 Influenza A virus (A/duck/Guangxi/1436/2006(H5... 26.3 2.2
gbEF124331.1 Influenza A virus (A/duck/Guangxi/1258/2006(H5... 26.3 2.2
gbEF124330.1 Influenza A virus (A/chicken/Guangxi/1212/2006... 26.3 2.2
gbEF124328.1 Influenza A virus (A/goose/Guiyang/4180/2005(H... 26.3 2.2
gbEF124327.1 Influenza A virus (A/chicken/Guiyang/1655/2006... 26.3 2.2
gbEF124325.1 Influenza A virus (A/goose/Shantou/3624/2006(H... 26.3 2.2
gbEF124324.1 Influenza A virus (A/duck/Guiyang/1081/2006(H5... 26.3 2.2
gbEF124323.1 Influenza A virus (A/goose/Guiyang/765/2006(H5... 26.3 2.2
gbEF124321.1 Influenza A virus (A/goose/Guiyang/1794/2006(H... 26.3 2.2
gbEF124320.1 Influenza A virus (A/duck/Guiyang/1722/2006(H5... 26.3 2.2
gbEF124319.1 Influenza A virus (A/goose/Guiyang/1636/2006(H... 26.3 2.2
gbEF124318.1 Influenza A virus (A/duck/Guiyang/1558/2006(H5... 26.3 2.2
gbEF124317.1 Influenza A virus (A/goose/Guiyang/1461/2006(H... 26.3 2.2
gbEF124316.1 Influenza A virus (A/duck/Fujian/10389/2005(H5... 26.3 2.2
gbEF124315.1 Influenza A virus (A/duck/Fujian/10160/2005(H5... 26.3 2.2
gbEF124314.1 Influenza A virus (A/goose/Guiyang/4030/2005(H... 26.3 2.2
gbEF124313.1 Influenza A virus (A/chicken/Guiyang/3923/2005... 26.3 2.2
gbEF124312.1 Influenza A virus (A/goose/Shantou/2086/2006(H... 26.3 2.2
gbEF124311.1 Influenza A virus (A/goose/Shantou/239/2006(H5... 26.3 2.2
gbEF124308.1 Influenza A virus (A/chicken/Guiyang/3570/2005... 26.3 2.2
gbEF124307.1 Influenza A virus (A/goose/Guiyang/3422/2005(H... 26.3 2.2
gbEF124306.1 Influenza A virus (A/duck/Guiyang/3242/2005(H5... 26.3 2.2
gbEF124305.1 Influenza A virus (A/chicken/Guiyang/3055/2005... 26.3 2.2
gbEF124304.1 Influenza A virus (A/duck/Guiyang/3009/2005(H5... 26.3 2.2
gbEF124303.1 Influenza A virus (A/duck/Guiyang/3996/2005(H5... 26.3 2.2
gbEF124302.1 Influenza A virus (A/duck/Guiyang/3834/2005(H5... 26.3 2.2
gbEF124299.1 Influenza A virus (A/duck/Yunnan/6332/2005(H5N... 26.3 2.2
gbEF124298.1 Influenza A virus (A/goose/Yunnan/6027/2005(H5... 26.3 2.2
gbEF124297.1 Influenza A virus (A/duck/Yunnan/5877/2005(H5N... 26.3 2.2
gbEF124296.1 Influenza A virus (A/goose/Yunnan/4804/2005(H5... 26.3 2.2
gbEF124295.1 Influenza A virus (A/duck/Yunnan/4589/2005(H5N... 26.3 2.2
gbEF124294.1 Influenza A virus (A/goose/Yunnan/4494/2005(H5... 26.3 2.2
gbEF124293.1 Influenza A virus (A/duck/Yunnan/4400/2005(H5N... 26.3 2.2
gbEF124292.1 Influenza A virus (A/goose/Yunnan/4129/2005(H5... 26.3 2.2
gbEF124291.1 Influenza A virus (A/goose/Yunnan/3720/2005(H5... 26.3 2.2
gbEF124290.1 Influenza A virus (A/duck/Guangxi/4665/2005(H5... 26.3 2.2
gbEF124289.1 Influenza A virus (A/duck/Guangxi/4196/2005(H5... 26.3 2.2
gbEF124288.1 Influenza A virus (A/duck/Guangxi/4184/2005(H5... 26.3 2.2
gbEF124287.1 Influenza A virus (A/duck/Guangxi/4016/2005(H5... 26.3 2.2
gbEF124286.1 Influenza A virus (A/duck/Guangxi/3819/2005(H5... 26.3 2.2
gbEF124285.1 Influenza A virus (A/chicken/Guangxi/3791/2005... 26.3 2.2
gbEF124284.1 Influenza A virus (A/duck/Guangxi/3741/2005(H5... 26.3 2.2
gbEF124283.1 Influenza A virus (A/goose/Guangxi/3714/2005(H... 26.3 2.2
gbEF124282.1 Influenza A virus (A/duck/Guangxi/3548/2005(H5... 26.3 2.2
gbEF124281.1 Influenza A virus (A/duck/Guangxi/3364/2005(H5... 26.3 2.2
gbEF124280.1 Influenza A virus (A/goose/Guangxi/3316/2005(H... 26.3 2.2
gbEF124279.1 Influenza A virus (A/chicken/Guangxi/3154/2005... 26.3 2.2
gbEF124278.1 Influenza A virus (A/duck/Guangxi/3085/2005(H5... 26.3 2.2
gbEF124277.1 Influenza A virus (A/goose/Guangxi/3017/2005(H... 26.3 2.2
gbEF124276.1 Influenza A virus (A/duck/Guangxi/2926/2005(H5... 26.3 2.2
gbEF124274.1 Influenza A virus (A/chicken/Guangxi/683/2006(... 26.3 2.2
gbEF124273.1 Influenza A virus (A/goose/Guangxi/532/2006(H5... 26.3 2.2
gbEF124272.1 Influenza A virus (A/chicken/Guangxi/463/2006(... 26.3 2.2
gbEF124271.1 Influenza A virus (A/duck/Fujian/720/2006(H5N1... 26.3 2.2
gbEF124270.1 Influenza A virus (A/duck/Fujian/671/2006(H5N1... 26.3 2.2
gbEF124269.1 Influenza A virus (A/duck/Fujian/668/2006(H5N1... 26.3 2.2
gbEF124268.1 Influenza A virus (A/chicken/Fujian/584/2006(H... 26.3 2.2
gbEF124267.1 Influenza A virus (A/duck/Fujian/12032/2005(H5... 26.3 2.2
gbEF124266.1 Influenza A virus (A/chicken/Fujian/11933/2005... 26.3 2.2
gbEF124265.1 Influenza A virus (A/duck/Fujian/11311/2005(H5... 26.3 2.2
gbEF124264.1 Influenza A virus (A/duck/Fujian/11094/2005(H5... 26.3 2.2
gbEF124263.1 Influenza A virus (A/duck/Fujian/10934/2005(H5... 26.3 2.2
gbEF124262.1 Influenza A virus (A/chicken/Fujian/10567/2005... 26.3 2.2
gbEF124261.1 Influenza A virus (A/chicken/Fujian/10313/2005... 26.3 2.2
gbEF124260.1 Influenza A virus (A/chicken/Fujian/10039/2005... 26.3 2.2
gbEF124259.1 Influenza A virus (A/chicken/Fujian/9821/2005(... 26.3 2.2
gbEF124258.1 Influenza A virus (A/duck/Fujian/9713/2005(H5N... 26.3 2.2
gbEF124257.1 Influenza A virus (A/duck/Fujian/9651/2005(H5N... 26.3 2.2
gbEF124256.1 Influenza A virus (A/duck/Hunan/988/2006(H5N1)... 26.3 2.2
gbEF124255.1 Influenza A virus (A/duck/Hunan/856/2006(H5N1)... 26.3 2.2
gbEF124254.1 Influenza A virus (A/duck/Hunan/344/2006(H5N1)... 26.3 2.2
gbEF124253.1 Influenza A virus (A/duck/Hunan/324/2006(H5N1)... 26.3 2.2
gbEF124252.1 Influenza A virus (A/duck/Hunan/5472/2005(H5N1... 26.3 2.2
gbEF124251.1 Influenza A virus (A/duck/Hunan/5152/2005(H5N1... 26.3 2.2
gbEF124250.1 Influenza A virus (A/duck/Hunan/5106/2005(H5N1... 26.3 2.2
gbEF124247.1 Influenza A virus (A/goose/Shantou/3295/2006(H... 26.3 2.2
gbEF124246.1 Influenza A virus (A/goose/Shantou/3265/2006(H... 26.3 2.2
gbEF124245.1 Influenza A virus (A/chicken/Shantou/1233/2006... 26.3 2.2
gbEF124244.1 Influenza A virus (A/goose/Shantou/18442/2005(... 26.3 2.2
gbEF124243.1 Influenza A virus (A/duck/Shantou/13323/2005(H... 26.3 2.2
gbEF124242.1 Influenza A virus (A/goose/Guiyang/538/2006(H5... 26.3 2.2
gbEF124241.1 Influenza A virus (A/duck/Guiyang/497/2006(H5N... 26.3 2.2
gbEF124240.1 Influenza A virus (A/duck/Guiyang/293/2006(H5N... 26.3 2.2
gbEF124239.1 Influenza A virus (A/chicken/Guiyang/29/2006(H... 26.3 2.2
gbEF124238.1 Influenza A virus (A/chicken/Guiyang/4059/2005... 26.3 2.2
gbEF124237.1 Influenza A virus (A/chicken/Guiyang/3721/2005... 26.3 2.2
gbEF124236.1 Influenza A virus (A/duck/Guangxi/804/2006(H5N... 26.3 2.2
gbEF124235.1 Influenza A virus (A/duck/Guangxi/744/2006(H5N... 26.3 2.2
gbEF124234.1 Influenza A virus (A/duck/Guangxi/619/2006(H5N... 26.3 2.2
gbEF124233.1 Influenza A virus (A/goose/Guangxi/582/2006(H5... 26.3 2.2
gbEF124232.1 Influenza A virus (A/duck/Guangxi/392/2006(H5N... 26.3 2.2
gbEF124231.1 Influenza A virus (A/duck/Guangxi/288/2006(H5N... 26.3 2.2
gbEF124230.1 Influenza A virus (A/goose/Guangxi/224/2006(H5... 26.3 2.2
gbEF124229.1 Influenza A virus (A/duck/Guangxi/150/2006(H5N... 26.3 2.2
gbEF124228.1 Influenza A virus (A/duck/Guangxi/5457/2005(H5... 26.3 2.2
gbEF124227.1 Influenza A virus (A/goose/Guangxi/5414/2005(H... 26.3 2.2
gbEF124226.1 Influenza A virus (A/duck/Guangxi/5270/2005(H5... 26.3 2.2
gbEF124225.1 Influenza A virus (A/duck/Guangxi/5165/2005(H5... 26.3 2.2
gbEF124224.1 Influenza A virus (A/duck/Guangxi/5075/2005(H5... 26.3 2.2
gbEF124223.1 Influenza A virus (A/chicken/Guangxi/4989/2005... 26.3 2.2
gbEF124222.1 Influenza A virus (A/duck/Guangxi/4830/2005(H5... 26.3 2.2
gbEF124221.1 Influenza A virus (A/goose/Guangxi/4513/2005(H... 26.3 2.2
gbEF124220.1 Influenza A virus (A/duck/Guangxi/4428/2005(H5... 26.3 2.2
gbEF124219.1 Influenza A virus (A/goose/Guangxi/4289/2005(H... 26.3 2.2
gbEF124216.1 Influenza A virus (A/duck/Yunnan/6607/2005(H5N... 26.3 2.2
gbEF124215.1 Influenza A virus (A/goose/Yunnan/6368/2005(H5... 26.3 2.2
gbEF124214.1 Influenza A virus (A/duck/Yunnan/5820/2005(H5N... 26.3 2.2
gbEF124213.1 Influenza A virus (A/duck/Yunnan/5251/2005(H5N... 26.3 2.2
gbEF124212.1 Influenza A virus (A/pheasant/Shantou/2239/200... 26.3 2.2
gbEF124211.1 Influenza A virus (A/chicken/Guiyang/2173/2005... 26.3 2.2
gbEF124210.1 Influenza A virus (A/chicken/Guiyang/2147/2005... 26.3 2.2
gbEF124209.1 Influenza A virus (A/duck/Guangxi/89/2006(H5N1... 26.3 2.2
gbEF124203.1 Influenza A virus (A/common magpie/Hong Kong/6... 26.3 2.2
gbEF124202.1 Influenza A virus (A/crested myna/Hong Kong/54... 26.3 2.2
gbEF124201.1 Influenza A virus (A/magpie robin/Hong Kong/36... 26.3 2.2
gbEF124200.1 Influenza A virus (A/chicken/Hong Kong/282/200... 26.3 2.2
gbEF124199.1 Influenza A virus (A/magpie robin/Hong Kong/75... 26.3 2.2
gbEF124198.1 Influenza A virus (A/common magpie/Hong Kong/3... 26.3 2.2
gbEF124197.1 Influenza A virus (A/house crow/Hong Kong/2858... 26.3 2.2
gbEF124196.1 Influenza A virus (A/house crow/Hong Kong/2648... 26.3 2.2
gbEF124195.1 Influenza A virus (A/large-billed crow/Hong Ko... 26.3 2.2
gbEF124194.1 Influenza A virus (A/white-backed munia/Hong K... 26.3 2.2
g
that's a good thing.
http://www.recombinomics.com/News/03230801/H274Y_Dogma.htmlCommentary (http://www.recombinomics.com/feed.xml) [/URL]
Tamiflu Resistance Challenges Influenza Genetics Dogma
Recombinomics Commentary 01:49
March 23, 2008
The recently released [URL="http://www.recombinomics.com/News/03220801/H274Y_US_Independent.html"]sequences (http://www.newsnow.co.uk/nn/Recombinomics) from H1N1 seasonal flu isolates in the United States by the Centers for Disease Control (CDC) further challenge the influenza genetics dogma, which maintains that such evolution is driven by selection of random mutations. Conceptually, such selection is easily understood when the virus is under attack by antivirals, such as oseltamivir (Tamiflu). Virus which randomly created the mutation which codes for H724Y would be about 1000 fold more efficient at budding from an infected cell, and therefore would have a strong selection advantage.
However, the sudden appearance (http://www.recombinomics.com/News/02150801/H274Y_Concurrent.html) of the resistance was in countries which usually did not use Tamiflu, in patients who had not been treated with Tamiflu eliminates the antiviral selection. Prior studies had indicated that H274Y would make the virus less fit, so the selective advantage in Tamiflu treated patients would not exist in influenza infected patients who were not under treatment, but the levels H274Y in almost 70% of H1N1 in Norway (http://www.who.int/csr/disease/influenza/resistanceweb20080320.pdf) clearly indicated that H1N1 with H274Y was evolutionarily fit.
This fitness was supported by the recently released sequences by the CDC. All were the Brisbayne/59 strain and mapped to the same branch of an H1N1 phylogenetic tree (for both NA and HA) and in many cases the NA `sequences were identical, indicating the resistant strain could spread across the country (multiple sequences were released from Arizona in the west and New Jersey in the east).
However, other isolates with H274Y mapped to another branch composed of isolates from western states (Hawaii and California), while other (http://www.recombinomics.com/News/01290802/H1N1_Tamiflu_US.html) resistant strains were the genetically distinct New Caledonia strain, which was more prevalent in prior years. Thus, not only was the resistant H1N1 evolutionarily fit, but it was formed via multiple independent introductions (at least three in the small number of positives from the US).
Moreover, like the isolates in Europe, the increase in resistance was sudden. Some isolates were identified last season, but the vast majority was from this season, which is also true for countries in Europe, which began to report the detection when multiple isolates from Norway were resistant.
The above scenario is difficult to explain by random mutations, even if a “fitness” mutation was widespread and help the resistant strains compete, because the sudden appearance does not correlate with countries that commonly use Tamiflu or recently increased the use of Tamiflu.
However, the change in Tamiflu usage preceding the sudden increase in H274Y in seasonal flu is found in the increased use of Tamiflu to treat H5N1. Although Tamiflu can inhibit the neuraminidase in all nine serotypes, it is less effective in N1. Moreover, it is less effective in H5N1 than H1N1, and in Tamiflu blanket applications, it is used at half the treatment dosage. This set of circumstances lead to the report of Tamiflu resistance Vietnam in 2005 and the genetic change in H5N1 was identical (http://www.recombinomics.com/News/01300804/H1N1_H274Y_H5N1.html) to the change in H1N1.
Moreover, the Tamiflu resistance in Vietnam (http://www.recombinomics.com/News/12210503/H5N1_Fatal_Tamiflu_Resistance.html) was also associated with a reduced case fatality rate in northern Vietnam (http://www.recombinomics.com/News/05180505/H5N1_Emerging_Tamiflu_Resistance.html) in 2005. In the north, the fatality rate fell from 70% in 2004, to less than 10% in 2005. Moreover, the lower case fatality rate was coincident with more efficient transmission to humans, increasing the likelihood of co-infections of H5N1 and H1N1, including H5N1 with H274Y linked to Tamiflu blanket applications. Although clusters in northern Vietnam were larger, the efficiency of transmission human to human was still markedly below seasonal flu, but recombination in co-infected host would allow for the acquisition of H274Y by H1N1, which could then be more efficiently spread human to human.
In addition, H274Y could be acquired by additional H1 serotypes in birds and swine followed by acquisition of H1N1 at distant locations, such as Norway. In either case, the introduction of H274Y into the human population could then be followed by acquisition of H274Y by other strains via recombination, and would not require new selection of random mutations.
Moreover, the sudden appearance of H274Y in human populations would follow the sudden increase in Tamiflu treatment of H5N1 in multiple locations, including Vietnam, Indonesia, Turkey, and Egypt.
.
gbEU567014.1 Influenza A virus (A/New Jersey/06/2008(H1N1))... 71.9 9e-11
gbEU567009.1 Influenza A virus (A/Arizona/13/2007(H1N1)) se... 71.9 9e-11
gbEU567006.1 Influenza A virus (A/Arizona/14/2007(H1N1)) se... 71.9 9e-11
gbEU566999.1 Influenza A virus (A/Wisconsin/01/2008(H1N1)) ... 71.9 9e-11
gbEU566998.1 Influenza A virus (A/Maryland/04/2007(H1N1)) s... 71.9 9e-11
gbEU566987.1 Influenza A virus (A/New Jersey/20/2007(H1N1))... 71.9 9e-11
gbEU566983.1 Influenza A virus (A/New Jersey/05/2008(H1N1))... 71.9 9e-11
gbEU566977.1 Influenza A virus (A/Pennsylvania/02/2008(H1N1... 71.9 9e-11
gbEU566968.1 Influenza A virus (A/Arizona/15/2007(H1N1)) se... 71.9 9e-11
gbEU516201.1 Influenza A virus (A/New Jersey/16/2007(H1N1))... 71.9 9e-11
gbEU516200.1 Influenza A virus (A/Illinois/10/2007(H1N1)) s... 71.9 9e-11
gbEU516196.1 Influenza A virus (A/Arizona/03/2007(H1N1)) se... 71.9 9e-11
gbEU516148.1 Influenza A virus (A/New Jersey/15/2007(H1N1))... 71.9 9e-11
gbEU516125.1 Influenza A virus (A/Hawaii/28/2007(H1N1)) seg... 71.9 9e-11
gbEU516123.1 Influenza A virus (A/Hawaii/28/2007(H1N1)) seg... 71.9 9e-11
gbEU516112.1 Influenza A virus (A/Hawaii/21/2007(H1N1)) seg... 71.9 9e-11
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