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  #1  
Old July 6th, 2009, 05:20 PM
HenryN HenryN is offline
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Breaking Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

Hong Kong has released the sequence of Tamiflu resistant NA.
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  #2  
Old July 6th, 2009, 05:20 PM
HenryN HenryN is offline
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Default Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

LOCUS GQ351316 1410 bp cRNA linear VRL 06-JUL-2009
DEFINITION Influenza A virus (A/Hong Kong/2369/2009(H1N1)) segment 6
neuraminidase (NA) gene, complete cds.
ACCESSION GQ351316
VERSION GQ351316.1 GI:251748197
DBLINK Project:37813
KEYWORDS .
SOURCE Influenza A virus (A/Hong Kong/2369/2009(H1N1))
ORGANISM Influenza A virus (A/Hong Kong/2369/2009(H1N1))
Viruses; ssRNA negative-strand viruses; Orthomyxoviridae;
Influenzavirus A.
REFERENCE 1 (bases 1 to 1410)
AUTHORS Tai,A.L.S., Cheng,P.K.C., Leung,T.W.C. and Lim,W.W.L.
TITLE Direct Submission
JOURNAL Submitted (05-JUL-2009) Virology Division, PHLSB, Centre for Health
Protection, 382 Nam Cheong Street, Shek Kip Mei, Kolwoon, Hong
Kong, China
COMMENT Swine influenza A (H1N1) virus isolated during human swine flu
outbreak of 2009.
FEATURES Location/Qualifiers
source 1..1410
/organism="Influenza A virus (A/Hong
Kong/2369/2009(H1N1))"
/mol_type="viral cRNA"
/strain="A/Hong Kong/2369/2009"
/serotype="H1N1"
/host="Homo sapiens"
/db_xref="taxon:657077"
/segment="6"
/country="China: Hong Kong"
/collection_date="11-Jun-2009"
/note="lineage: swl"
gene 1..1410
/gene="NA"
CDS 1..1410
/gene="NA"
/codon_start=1
/product="neuraminidase"
/protein_id="ACT10319.1"
/db_xref="GI:251748198"
/translation="MNPNQKIITIGSVCMTIGMANLILQIGNIISIWISHSIQLGNQN
QIETCNQSVITYENNTWVNQTYVNISNTNFAAGQSVVSVKLAGNSSLCPV SGWAIYSK
DNSIRIGSKGDVFVIREPFISCSPLECRTFFLTQGALLNDKHSNGTIKDR SPYRTLMS
CPIGEVPSPYNSRFESVAWSASACHDGINWLTIGISGPDNGAVAVLKYNG IITDTIKS
WRNNILRTQESECACVNGSCFTVMTDGPSDGQASYKIFRIEKGKIVKSVE MNAPNYYY
EECSCYPDSSEITCVCRDNWHGSNRPWVSFNQNLEYQIGYICSGIFGDNP RPNDKTGS
CGPVSSNGANGVKGFSFKYGNGVWIGRTKSISSRNGFEMIWDPNGWTGTD NNFSIKQD
IVGINEWSGYSGSFVQHPELTGLDCIRPCFWVELIRGRPKENTIWTSGSS ISFCGVNS
DTVGWSWPDGAELPFTIDK"
ORIGIN
1 atgaatccaa accaaaagat aataaccatt ggttcggtct gtatgacaat tggaatggct
61 aacttaatat tacaaattgg aaacataatc tcaatatgga ttagccactc aattcaactt
121 gggaatcaaa atcagattga aacatgcaat caaagcgtca ttacttatga aaacaacact
181 tgggtaaatc agacatatgt taacatcagc aacaccaact ttgctgctgg acagtcagtg
241 gtttccgtga aattagcggg caattcctct ctctgccctg ttagtggatg ggctatatac
301 agtaaagaca acagtataag aatcggttcc aagggggatg tgtttgtcat aagggaacca
361 ttcatatcat gctccccctt ggaatgcaga accttcttct tgactcaagg ggccttgcta
421 aatgacaaac attccaatgg aaccattaaa gacaggagcc catatcgaac cctaatgagc
481 tgtcctattg gtgaagttcc ctctccatac aactcaagat ttgagtcagt cgcttggtca
541 gcaagtgctt gtcatgatgg catcaattgg ctaacaattg gaatttctgg cccagacaat
601 ggggcagtgg ctgtgttaaa gtacaacggc ataataacag acactatcaa gagttggaga
661 aacaatatat tgagaacaca agagtctgaa tgtgcatgtg taaatggttc ttgctttact
721 gtaatgaccg atggaccaag tgatggacag gcctcataca agatcttcag aatagaaaag
781 ggaaagatag tcaaatcagt cgaaatgaat gcccctaatt attactatga ggaatgctcc
841 tgttatcctg attctagtga aatcacatgt gtatgcaggg ataactggca tggctcgaat
901 cgaccgtggg tgtctttcaa ccagaatctg gaatatcaga taggatacat atgcagtggg
961 attttcggag acaatccacg ccctaatgat aagacaggca gttgtggtcc agtatcgtct
1021 aatggagcaa atggagtaaa aggattttca ttcaaatacg gcaatggtgt ttggataggg
1081 agaactaaaa gcattagttc aagaaacggt tttgagatga tttgggatcc gaacggatgg
1141 actgggacag acaataactt ctcaataaag caagatatcg taggaataaa tgagtggtca
1201 ggatatagcg ggagttttgt tcagcatcca gaactaacag ggctggattg tataagacct
1261 tgcttctggg ttgaactaat cagagggcga cccaaagaga acacaatctg gactagcggg
1321 agcagcatat ccttttgtgg tgtaaacagt gacactgtgg gttggtcttg gccagacggt
1381 gctgagttgc catttaccat tgacaagtaa
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  #3  
Old July 6th, 2009, 05:21 PM
hawkeye hawkeye is offline
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Default Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

can't wait to hear the results.
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  #4  
Old July 6th, 2009, 05:28 PM
HenryN HenryN is offline
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Default Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

Jersey girl
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  #5  
Old July 6th, 2009, 05:30 PM
HenryN HenryN is offline
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Default Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

NA identical to sequence below (except for H274Y)

LOCUS GQ160533 1410 bp cRNA linear VRL 15-MAY-2009
DEFINITION Influenza A virus (A/New Jersey/01/2009(H1N1)) segment 6
neuraminidase (NA) gene, complete cds.
ACCESSION GQ160533
VERSION GQ160533.1 GI:237651369
DBLINK Project:37813
KEYWORDS .
SOURCE Influenza A virus (A/New Jersey/01/2009(H1N1))
ORGANISM Influenza A virus (A/New Jersey/01/2009(H1N1))
Viruses; ssRNA negative-strand viruses; Orthomyxoviridae;
Influenzavirus A.
REFERENCE 1 (bases 1 to 1410)
AUTHORS Shu,B., Balish,A., Garten,R., Smith,C., Emery,S., Barnes,J.,
Deyde,V., Klimov,A. and Cox,N.
TITLE Human infection with novel swine H1N1 influenza
JOURNAL Unpublished
REFERENCE 2 (bases 1 to 1410)
AUTHORS Shu,B., Balish,A., Garten,R., Smith,C., Emery,S., Barnes,J.,
Deyde,V., Klimov,A. and Cox,N.
TITLE Direct Submission
JOURNAL Submitted (14-MAY-2009) WHO Collaborating Center for Surveillance,
Epidemiology and Control of Influenza, Influenza Division, Centers
for Disease Control and Prevention, 1600 Clifton Road, N.E.,
Atlanta, GA 30333, USA
COMMENT Swine influenza A (H1N1) virus isolated during human swine flu
outbreak of 2009. For more information, see http://www.cdc.gov/.

Some of the information does not have GenBank feature identifiers
and is being provided in the comment section.

##EpifluData-START##
Isolate A/New Jersey/01/2009
Subtype H1N1
Segment_name NA
Host_gender F
Host_age 12
Passage_history C1
Adamantane_resistance resistant
Zanamivir_resistance sensitive
Oseltamivir_resistance sensitive
Country USA
State/Province New Jersey state
Collection_month 4
Collection_year 2009
EPI_accession EPI179148
##EpifluData-END##
FEATURES Location/Qualifiers
source 1..1410
/organism="Influenza A virus (A/New Jersey/01/2009(H1N1))"
/mol_type="viral cRNA"
/strain="A/New Jersey/01/2009"
/serotype="H1N1"
/host="Homo sapiens; gender F; age 12"
/db_xref="taxon:645236"
/segment="6"
/country="USA:New Jersey state"
/collection_date="Apr-2009"
gene 1..1410
/gene="NA"
CDS 1..1410
/gene="NA"
/codon_start=1
/product="neuraminidase"
/protein_id="ACR08567.1"
/db_xref="GI:237651370"
/translation="MNPNQKIITIGSVCMTIGMANLILQIGNIISIWISHSIQLGNQN
QIETCNQSVITYENNTWVNQTYVNISNTNFAAGQSVVSVKLAGNSSLCPV SGWAIYSK
DNSIRIGSKGDVFVIREPFISCSPLECRTFFLTQGALLNDKHSNGTIKDR SPYRTLMS
CPIGEVPSPYNSRFESVAWSASACHDGINWLTIGISGPDNGAVAVLKYNG IITDTIKS
WRNNILRTQESECACVNGSCFTVMTDGPSDGQASYKIFRIEKGKIVKSVE MNAPNYHY
EECSCYPDSSEITCVCRDNWHGSNRPWVSFNQNLEYQIGYICSGIFGDNP RPNDKTGS
CGPVSSNGANGVKGFSFKYGNGVWIGRTKSISSRNGFEMIWDPNGWTGTD NNFSIKQD
IVGINEWSGYSGSFVQHPELTGLDCIRPCFWVELIRGRPKENTIWTSGSS ISFCGVNS
DTVGWSWPDGAELPFTIDK"
ORIGIN
1 atgaatccaa accaaaagat aataaccatt ggttcggtct gtatgacaat tggaatggct
61 aacttaatat tacaaattgg aaacataatc tcaatatgga ttagccactc aattcaactt
121 gggaatcaaa atcagattga aacatgcaat caaagcgtca ttacttatga aaacaacact
181 tgggtaaatc agacatatgt taacatcagc aacaccaact ttgctgctgg acagtcagtg
241 gtttccgtga aattagcggg caattcctct ctctgccctg ttagtggatg ggctatatac
301 agtaaagaca acagtataag aatcggttcc aagggggatg tgtttgtcat aagggaacca
361 ttcatatcat gctccccctt ggaatgcaga accttcttct tgactcaagg ggccttgcta
421 aatgacaaac attccaatgg aaccattaaa gacaggagcc catatcgaac cctaatgagc
481 tgtcctattg gtgaagttcc ctctccatac aactcaagat ttgagtcagt cgcttggtca
541 gcaagtgctt gtcatgatgg catcaattgg ctaacaattg gaatttctgg cccagacaat
601 ggggcagtgg ctgtgttaaa gtacaacggc ataataacag acactatcaa gagttggaga
661 aacaatatat tgagaacaca agagtctgaa tgtgcatgtg taaatggttc ttgctttact
721 gtaatgaccg atggaccaag tgatggacag gcctcataca agatcttcag aatagaaaag
781 ggaaagatag tcaaatcagt cgaaatgaat gcccctaatt atcactatga ggaatgctcc
841 tgttatcctg attctagtga aatcacatgt gtatgcaggg ataactggca tggctcgaat
901 cgaccgtggg tgtctttcaa ccagaatctg gaatatcaga taggatacat atgcagtggg
961 attttcggag acaatccacg ccctaatgat aagacaggca gttgtggtcc agtatcgtct
1021 aatggagcaa atggagtaaa aggattttca ttcaaatacg gcaatggtgt ttggataggg
1081 agaactaaaa gcattagttc aagaaacggt tttgagatga tttgggatcc gaacggatgg
1141 actgggacag acaataactt ctcaataaag caagatatcg taggaataaa tgagtggtca
1201 ggatatagcg ggagttttgt tcagcatcca gaactaacag ggctggattg tataagacct
1261 tgcttctggg ttgaactaat cagagggcga cccaaagaga acacaatctg gactagcggg
1321 agcagcatat ccttttgtgg tgtaaacagt gacactgtgg gttggtcttg gccagacggt
1381 gctgagttgc catttaccat tgacaagtaa
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  #6  
Old July 6th, 2009, 05:32 PM
HenryN HenryN is offline
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Default Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

Quote:
Originally Posted by hawkeye View Post
can't wait to hear the results.
Hopes and dreams of reassorters dashed. It is swine NA, and exactly matches NJ isolate and only one difference (besides H274Y) with larger series.
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  #7  
Old July 6th, 2009, 05:45 PM
vinny vinny is offline
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Default Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

Is it tamiflu resistant Dr niman....?,thanks.
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  #8  
Old July 6th, 2009, 05:54 PM
HenryN HenryN is offline
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Default Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

Quote:
Originally Posted by vinny View Post
Is it tamiflu resistant Dr niman....?,thanks.
Only the Hong Kong sequence has H274Y.
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  #9  
Old July 6th, 2009, 05:57 PM
HenryN HenryN is offline
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Default Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

Travel log of polymorphism shared with NJ (and OK) in pandemic H1N1.

gb|GQ338380.1| Influenza A virus (A/Oklahoma/03/2009(H1N1)) s... 30.2 45
gb|CY041452.1| Influenza A virus (A/California/UR06-0439/2007... 30.2 45
gb|GQ160533.1| Influenza A virus (A/New Jersey/01/2009(H1N1))... 30.2 45
gb|CY032399.1| Influenza A virus (A/equine/Sao Paulo/1/1969(H... 30.2 45
gb|CY032295.1| Influenza A virus (A/equine/Sao Paulo/6/1963(H... 30.2 45
gb|EU409969.1| Influenza A virus (A/swine/Ohio/K1207/06(H1N1)... 30.2 45
gb|EU516136.1| Influenza A virus (A/New Mexico/05/2007(H1N1))... 30.2 45
gb|EU516135.1| Influenza A virus (A/Alaska/01/2007(H1N1)) seg... 30.2 45
gb|EU429796.1| Influenza A virus (A/chicken/Germany/N/1949(H1... 30.2 45
gb|CY028774.1| Influenza A virus (A/Virginia/UR06-0361/2007(H... 30.2 45
gb|CY028461.1| Influenza A virus (A/California/UR06-0442/2007... 30.2 45
gb|CY028421.1| Influenza A virus (A/Illinois/UR06-0215/2007(H... 30.2 45
gb|CY028405.1| Influenza A virus (A/Ohio/UR06-0429/2007(H1N1)... 30.2 45
gb|EU158122.1| Influenza A virus (A/mallard/Italy/250/02(H7N1... 30.2 45
gb|CY028149.1| Influenza A virus (A/Kentucky/UR06-0182/2007(H... 30.2 45
gb|CY028141.1| Influenza A virus (A/Kansas/UR06-0191/2007(H1N... 30.2 45
gb|CY028069.1| Influenza A virus (A/Illinois/UR06-0093/2007(H... 30.2 45
gb|CY027941.1| Influenza A virus (A/Virginia/UR06-0295/2007(H... 30.2 45
gb|CY027845.1| Influenza A virus (A/California/UR06-0125/2007... 30.2 45
gb|CY027821.1| Influenza A virus (A/Illinois/UR06-0074/2007(H... 30.2 45
gb|CY027765.1| Influenza A virus (A/Ohio/UR06-0112/2007(H1N1)... 30.2 45
gb|CY027709.1| Influenza A virus (A/Virginia/UR06-0549/2007(H... 30.2 45
gb|CY027701.1| Influenza A virus (A/Illinois/UR06-0131/2007(H... 30.2 45
gb|CY027677.1| Influenza A virus (A/Kentucky/UR06-0449/2007(H... 30.2 45
gb|CY027373.1| Influenza A virus (A/Kentucky/UR06-0424/2007(H... 30.2 45
gb|CY027485.1| Influenza A virus (A/Illinois/UR06-0115/2007(H... 30.2 45
gb|CY027469.1| Influenza A virus (A/Ohio/UR06-0394/2007(H1N1)... 30.2 45
gb|CY027437.1| Influenza A virus (A/Illinois/UR06-0094/2007(H... 30.2 45
gb|CY027421.1| Influenza A virus (A/Tennessee/UR06-0262/2007(... 30.2 45
gb|CY027397.1| Influenza A virus (A/Illinois/UR06-0136/2007(H... 30.2 45
gb|CY027357.1| Influenza A virus (A/California/UR06-0564/2007... 30.2 45
gb|CY027277.1| Influenza A virus (A/Illinois/UR06-0116/2007(H... 30.2 45
gb|CY027245.1| Influenza A virus (A/Tennessee/UR06-0124/2007(... 30.2 45
gb|CY027237.1| Influenza A virus (A/Virginia/UR06-0117/2007(H... 30.2 45
gb|CY027229.1| Influenza A virus (A/Colorado/UR06-0499/2007(H... 30.2 45
gb|CY027213.1| Influenza A virus (A/California/UR06-0585/2007... 30.2 45
gb|CY027149.1| Influenza A virus (A/North Carolina/UR06-0011/... 30.2 45
gb|CY027141.1| Influenza A virus (A/Ohio/UR06-0177/2007(H1N1)... 30.2 45
gb|CY027093.1| Influenza A virus (A/Illinois/UR06-0137/2007(H... 30.2 45
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  #10  
Old July 6th, 2009, 06:06 PM
hawkeye hawkeye is offline
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Default Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

thanks!
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  #11  
Old July 6th, 2009, 06:16 PM
JJackson JJackson is offline
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Default Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

If it is YHY rather than YYY what is conferring the resistance?
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  #12  
Old July 6th, 2009, 06:24 PM
pjie2 pjie2 is offline
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Default Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

Quote:
Originally Posted by niman View Post
Hopes and dreams of reassorters dashed. It is swine NA, and exactly matches NJ isolate and only one difference (besides H274Y) with larger series.
Hmmm. Is it a recombinant? If it's a recombinant, what did it recombine with in order to acquire H274Y? If there aren't any flanking polymorphisms that are derived from a different strain, how can you tell the difference between recombination and de novo mutation?
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  #13  
Old July 6th, 2009, 06:47 PM
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Default Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

Did anyone in her family, or any traveling HK acquaintances, have a lingering seasonal H1N1 from HK - thereby setting the stage for a dual infection?

.
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  #14  
Old July 6th, 2009, 07:00 PM
HenryN HenryN is offline
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Default Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

Quote:
Originally Posted by JJackson View Post
If it is YHY rather than YYY what is conferring the resistance?
There is only one resistant sequence (from Hong Kong). The NJ sequence matches at all other positions.
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  #15  
Old July 6th, 2009, 07:03 PM
HenryN HenryN is offline
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Default Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

Quote:
Originally Posted by pjie2 View Post
Hmmm. Is it a recombinant? If it's a recombinant, what did it recombine with in order to acquire H274Y? If there aren't any flanking polymorphisms that are derived from a different strain, how can you tell the difference between recombination and de novo mutation?
Coincidences get very old very fast. The recombination leads to exchanges of SNPs, as described in the Nature Precedings paper. The donor sequence would be seasonal H1N1, which matches on the 3' side (like A/Indiana/1/2008).
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  #16  
Old July 6th, 2009, 07:07 PM
JJackson JJackson is offline
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Default Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

Thanks. Sorry did not read closely enough just looked at the sequences. You were just giving Jersey Girl as a close pre change relative.
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  #17  
Old July 6th, 2009, 07:07 PM
HenryN HenryN is offline
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Default Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

Quote:
Originally Posted by pjie2 View Post
Hmmm. Is it a recombinant? If it's a recombinant, what did it recombine with in order to acquire H274Y? If there aren't any flanking polymorphisms that are derived from a different strain, how can you tell the difference between recombination and de novo mutation?
Here is the H274Y travel log (sequences that can donate H274Y)

gb|EU567011.1| Influenza A virus (A/Indiana/01/2008(H1N1)) se... 36.2 0.73
gb|DQ493078.1| Influenza A virus (A/Vietnam/CL2009/2005(H5N1)... 36.2 0.73
gb|DQ250165.1| Influenza A virus (A/Vietnam/CL2009/2005(H5N1)... 36.2 0.73
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  #18  
Old July 6th, 2009, 07:08 PM
HenryN HenryN is offline
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Default Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

Quote:
Originally Posted by JJackson View Post
Thanks. Sorry did not read closely enough just looked at the sequences. You were just giving Jersey Girl as a close pre change relative.
Identical pre-change in NA (also has one of the three HA polymorphisms).
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  #19  
Old July 6th, 2009, 07:10 PM
HenryN HenryN is offline
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Default Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

Quote:
Originally Posted by AlaskaDenise View Post
Did anyone in her family, or any traveling HK acquaintances, have a lingering seasonal H1N1 from HK - thereby setting the stage for a dual infection?

.
There is no evidence that the recombination happened in San Francisco. Pandemic H1N1 with H274Y is FIT and circulating below the radar (in MILD cases).
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  #20  
Old July 6th, 2009, 07:18 PM
HenryN HenryN is offline
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Default Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

Quote:
Originally Posted by pjie2 View Post
Hmmm. Is it a recombinant? If it's a recombinant, what did it recombine with in order to acquire H274Y? If there aren't any flanking polymorphisms that are derived from a different strain, how can you tell the difference between recombination and de novo mutation?
The donor sequence was described last year (before the pandemic H1N1 was known)

Commentary

.
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  #21  
Old July 6th, 2009, 07:20 PM
HenryN HenryN is offline
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Default Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

Quote:
Originally Posted by pjie2 View Post
Hmmm. Is it a recombinant? If it's a recombinant, what did it recombine with in order to acquire H274Y? If there aren't any flanking polymorphisms that are derived from a different strain, how can you tell the difference between recombination and de novo mutation?
Here is a description from last year (BEFORE pandemic H1N1 emerged)


The ability of H274Y to jump from clade to clade, as well as multiple sub-clades in 2B, as well as the rapid evolution of the 2B sub-clades, raises concerns of another vaccine mismatch, as well as the associated increase in H274Y in the H1N1 gene pool. Moreover, the match between H5N1 and the recent H1N1 isolate from Indiana raises concerns that oseltamivir resistance would develop quickly after H5N1 transmission efficiencies in humans increase, regardless of oseltamivir usage.

The rapid spread of H274Y in seasonal flu and the recent reports of increases to 100% continue to be cause for concern in seasonal and pandemic flu evolution and spread.


Commentary

.
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  #22  
Old July 6th, 2009, 07:25 PM
English Teacher English Teacher is offline
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Default Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

I know that this isn't a discussion board, so I'd like to ask Dr. Niman if he will start a thread over there to explain this to the laymen like me. It seems very important, but I don't understand anything except that the H1N1 has developed a resistance to Tamiflu? Thanks.
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  #23  
Old July 6th, 2009, 07:29 PM
HenryN HenryN is offline
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Default Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

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Originally Posted by English Teacher View Post
I know that this isn't a discussion board, so I'd like to ask Dr. Niman if he will start a thread over there to explain this to the laymen like me. It seems very important, but I don't understand anything except that the H1N1 has developed a resistance to Tamiflu? Thanks.
Since this is just a pseudo news thread because the media hasn't figured out that the sequences have been released, and the "experts" really don't want to talk about the sequences because this is no reassortment involving human H1N1 with H274Y and no Tamiflu to select H274Y, I think a discussion can carry this thread forward.
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Old July 6th, 2009, 07:32 PM
HenryN HenryN is offline
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Default Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

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Originally Posted by English Teacher View Post
I know that this isn't a discussion board, so I'd like to ask Dr. Niman if he will start a thread over there to explain this to the laymen like me. It seems very important, but I don't understand anything except that the H1N1 has developed a resistance to Tamiflu? Thanks.
You are correct. This IS very important (and will NOT be explained in the media or by the "experts" who were "puzzled" by the H274Y in seasonal flu, and there were no lessons learned, because they are spouting the same nonsense about "random mutations" and reassortment to explain H274Y in H1N1 pandemic flu, neither of which explains the Hong Kong sequence or circumstances.
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Old July 6th, 2009, 07:40 PM
JJackson JJackson is offline
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Default Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

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There is no evidence that the recombination happened in San Francisco. Pandemic H1N1 with H274Y is FIT and circulating below the radar (in MILD cases).
Sorry to be lazy and pick your brains but I have not looked at the HA sequences. You say the H1N1(2009) is FIT and there are HA changes. What are you basing your fitness on? Is one of the change A193T?
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Old July 6th, 2009, 07:40 PM
HenryN HenryN is offline
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Default Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

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Originally Posted by English Teacher View Post
I know that this isn't a discussion board, so I'd like to ask Dr. Niman if he will start a thread over there to explain this to the laymen like me. It seems very important, but I don't understand anything except that the H1N1 has developed a resistance to Tamiflu? Thanks.
Briefly, H274Y in H1N1 seasonal flu could not be explained by the two pillars of influenza genetics, drift by random mutation introduced by copy errors, and shifts by reassortment.

The H274Y jumped from genetic background to genetic background, eliminating reassortment, but "random errors" made no sense because there was no involvement of Tamiflu, and Tamiflu causes other resisatnce changes in H1N1 and H3N2, but all resistance was linked H274Y in H1N1. Moreover, the emergence of H274Y in the Brisbane strain (clade 2B) was linked to additional acquistions, and the key acquistions were in clade 2C (Hong Kong strain) which was co-circulating.

The acquistions in seasonal flu were detailed here

http://precedings.nature.com/documents/2832/version/1

and were due to genetic hitchhiking and recombination - and the gateway from H274Y in H5N1 and H274Y in H1N1 was the Indiana seasonal flu sequence, which was the same gateway used to move H274Y from seasonal H1N1 to pandemic (swine) H1N1.
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Old July 6th, 2009, 07:43 PM
HenryN HenryN is offline
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Default Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

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Sorry to be lazy and pick your brains but I have not looked at the HA sequences. You say the H1N1(2009) is FIT and there are HA changes. What are you basing your fitness on? Is one of the change A193T?
Fitness is based on infection of Hong Kong teenage who was not taking Tamiflu.
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Old July 6th, 2009, 07:53 PM
HenryN HenryN is offline
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Default Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

I have to break for tonight, and have morning meetings, so I won't be participating much until tomorrow afternoon (but not for lack of interest).
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Old July 6th, 2009, 08:06 PM
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Default Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

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I know that this isn't a discussion board, so I'd like to ask Dr. Niman if he will start a thread over there to explain this to the laymen like me. It seems very important, but I don't understand anything except that the H1N1 has developed a resistance to Tamiflu? Thanks.
We can definitely discuss the science on this thread. Thanks for asking English Teacher.
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Old July 7th, 2009, 05:12 AM
HenryN HenryN is offline
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Default Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

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Originally Posted by English Teacher View Post
I know that this isn't a discussion board, so I'd like to ask Dr. Niman if he will start a thread over there to explain this to the laymen like me. It seems very important, but I don't understand anything except that the H1N1 has developed a resistance to Tamiflu? Thanks.
The real gateway between H274Y on H1N1 seasonal flu and moving it to H1N1 pandmeic flu is the sequence seen in Indiana last year. It had the key change that allowed H274Y to go from H5N1 to H1N1, and that same change allows for H274Y to go from seasonal H1N1 to pandemic H1N1.

Pandemic H1N1 can also get H274Y from H5N1 and some of the new polymorphisms on H1N1 link back to H5N1, which is why pandmeic H1N1 in countries like Egypt, Indonesia, Vietnam, and India may be major problems.
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