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PostPosted: Wed Jan 04, 2012 6:33 am 
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The WHO Chinese National Influenza Center in Beijing has released HA, NA, PB1, NP, and MP sequences (at GISAID) from the fatal H5N1 case (39M) in Shenzhen City, Guangdong Province in China (A/Guangdong-Shenzhen/1/2011).

The case has a large number of HA changes including Q196Q and S227R. It also has acquired an R in the HA cleavage site which is in recent wild bird and duck sequences.

These changes signal significant recombination and an increase in pandemic concerns.

http://www.recombinomics.com/News/01041 ... S227R.html
Q196K and S227R In Fatal H5N1 Case In Shenzhen China
Recombinomics Commentary 03:45
January 4, 2012

The WHO Chinese National Influenza Center in Beijing has released HA, NA, PB1, NP, and MP sequences from the fatal H5N1 case (39M) in Shenzhen City, Guangdong Province in China (A/Guangdong-Shenzhen/1/2011).

The WHO Chinese National Influenza Center is congratulated for its rapid release of these important sequences........

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PostPosted: Wed Jan 04, 2012 6:57 am 
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Sequences with matching HA cleavage site
EPI347304 A/Guangdong-Shenzhen/1/2011(H5N1) (A/H5N1) segment 4 (HA) 38.1 3.410302e-03 20/20 (100%)
EPI337217 A/Guangxi/1/2009 (A/H5N1) segment 4 (HA) 38.1 3.410302e-03 20/20 (100%)
EPI337002 A/duck/Zhejiang/2248/2011 (A/H5N1) segment 4 (HA) 38.1 3.410302e-03 20/20 (100%)
EPI337001 A/duck/Zhejiang/2245/2011 (A/H5N1) segment 4 (HA) 38.1 3.410302e-03 20/20 (100%)
EPI337000 A/duck/Zhejiang/2244/2011 (A/H5N1) segment 4 (HA) 38.1 3.410302e-03 20/20 (100%)
EPI336999 A/duck/Zhejiang/2243/2011 (A/H5N1) segment 4 (HA) 38.1 3.410302e-03 20/20 (100%)
EPI336998 A/duck/Zhejiang/2242/2011 (A/H5N1) segment 4 (HA) 38.1 3.410302e-03 20/20 (100%)
EPI336997 A/duck/Zhejiang/224/2011 (A/H5N1) segment 4 (HA) 38.1 3.410302e-03 20/20 (100%)
EPI336996 A/duck/Zhejiang/213/2011 (A/H5N1) segment 4 (HA) 38.1 3.410302e-03 20/20 (100%)
EPI330995 A/duck/Vietnam/NCVD-672/2011 (A/H5N1) segment 4 (HA) 38.1 3.410302e-03 20/20 (100%)
EPI321596 A/duck/Vietnam/27386/2009 (A/H5N1) segment 4 (HA) 38.1 3.410302e-03 20/20 (100%)
EPI321595 A/duck/Vietnam/27374/2009 (A/H5N1) segment 4 (HA) 38.1 3.410302e-03 20/20 (100%)
EPI321594 A/duck/Vietnam/27373/2009 (A/H5N1) segment 4 (HA) 38.1 3.410302e-03 20/20 (100%)
EPI321593 A/duck/Vietnam/27372/2009 (A/H5N1) segment 4 (HA) 38.1 3.410302e-03 20/20 (100%)
EPI321592 A/duck/Vietnam/27354/2009 (A/H5N1) segment 4 (HA) 38.1 3.410302e-03 20/20 (100%)
EPI321590 A/duck/Vietnam/27339/2009 (A/H5N1) segment 4 (HA) 38.1 3.410302e-03 20/20 (100%)
EPI321589 A/duck/Vietnam/27329/2009 (A/H5N1) segment 4 (HA) 38.1 3.410302e-03 20/20 (100%)
EPI321510 A/chicken/Vietnam/27265/2009 (A/H5N1) segment 4 (HA) 38.1 3.410302e-03 20/20 (100%)
EPI321504 A/chicken/Vietnam/20396/2009 (A/H5N1) segment 4 (HA) 38.1 3.410302e-03 20/20 (100%)
EPI321503 A/chicken/Vietnam/20395/2009 (A/H5N1) segment 4 (HA) 38.1 3.410302e-03 20/20 (100%)
EPI321502 A/chicken/Vietnam/20392/2009 (A/H5N1) segment 4 (HA) 38.1 3.410302e-03 20/20 (100%)
EPI321501 A/chicken/Vietnam/20390/2009 (A/H5N1) segment 4 (HA) 38.1 3.410302e-03 20/20 (100%)
EPI321500 A/chicken/Vietnam/20389/2009 (A/H5N1) segment 4 (HA) 38.1 3.410302e-03 20/20 (100%)
EPI321499 A/chicken/Vietnam/20388/2009 (A/H5N1) segment 4 (HA) 38.1 3.410302e-03 20/20 (100%)
EPI321497 A/chicken/Vietnam/20346/2009 (A/H5N1) segment 4 (HA) 38.1 3.410302e-03 20/20 (100%)
EPI320685 A/Muscovy duck/Vietnam/18153/2009 (A/H5N1) segment 4 (HA) 38.1 3.410302e-03 20/20 (100%)
EPI320684 A/Muscovy duck/Vietnam/18152/2009 (A/H5N1) segment 4 (HA) 38.1 3.410302e-03 20/20 (100%)
EPI320682 A/Muscovy duck/Vietnam/18151/2009 (A/H5N1) segment 4 (HA) 38.1 3.410302e-03 20/20 (100%)
EPI280088 A/Guangxi/1/2009 (A/H5N1) segment 4 (HA) 38.1 3.410302e-03 20/20 (100%)
EPI272143 A/chicken/Jiangxi/Q1/2008 (A/H5) segment 4 (HA) 38.1 3.410302e-03 20/20 (100%)
EPI272142 A/chicken/Guangdong/Q2/2008 (A/H5) segment 4 (HA) 38.1 3.410302e-03 20/20 (100%)
EPI254278 A/feral pigeon/Hong Kong/3409/2009 (A/H5N1) segment 4 (HA) 38.1 3.410302e-03 20/20 (100%)
EPI220563 A/house crow/Hong Kong/7677/2008 (A/H5N1) segment 4 (HA) 38.1 3.410302e-03 20/20 (100%)
EPI219335 A/large billed crow/Hong Kong/885/2009 (A/H5N1) segment 4 (HA) 38.1 3.410302e-03 20/20 (100%)
EPI219333 A/grey heron/Hong Kong/779/2009 (A/H5N1) segment 4 (HA) 38.1 3.410302e-03 20/20 (100%)
EPI219331 A/crested myna/Hong Kong/1178/2009 (A/H5N1) segment 4 (HA) 38.1 3.410302e-03 20/20 (100%)
EPI176348 A/Guangxi/1/2009 (A/H5N1) segment 4 (HA) 38.1 3.410302e-03 20/20 (100%)
EPI168056 A/magpie robin/Hong Kong/1897/2008 (A/H5N1) segment 4 (HA) 38.1 3.410302e-03 20/20 (100%)
EPI168048 A/magpie robin/Hong Kong/1097/2008 (A/H5N1) segment 4 (HA) 38.1 3.410302e-03 20/20 (100%)
EPI168040 A/grey heron/Hong Kong/1046/2008 (A/H5N1) segment 4 (HA) 38.1 3.410302e-03 20/20 (100%)
EPI168032 A/great egret/Hong Kong/807/2008 (A/H5N1) segment 4 (HA) 38.1 3.410302e-03 20/20 (100%)
EPI168008 A/grey heron/Hong Kong/3088/2007 (A/H5N1) segment 4 (HA) 38.1 3.410302e-03 20/20 (100%)

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PostPosted: Wed Jan 04, 2012 7:04 am 
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LOCUS CY098744 1745 bp cRNA linear VRL 29-NOV-2011
DEFINITION Influenza A virus (A/Guangxi/1/2009(H5N1)) hemagglutinin (HA) gene,
complete cds.
ACCESSION CY098744
VERSION CY098744.1 GI:347364488
KEYWORDS .
SOURCE Influenza A virus (A/Guangxi/1/2009(H5N1))
ORGANISM Influenza A virus (A/Guangxi/1/2009(H5N1))
Viruses; ssRNA negative-strand viruses; Orthomyxoviridae;
Influenzavirus A.
REFERENCE 1 (bases 1 to 1745)
AUTHORS Wan,X.F., Dong,L., Lan,Y., Long,L.P., Xu,C., Zou,S., Li,Z., Wen,L.,
Cai,Z., Wang,W., Li,X., Yuan,F., Sui,H., Zhang,Y., Dong,J., Sun,S.,
Gao,Y., Wang,M., Bai,T., Yang,L., Li,D., Yang,W., Yu,H., Wang,S.,
Feng,Z., Wang,Y., Guo,Y., Webby,R.J. and Shu,Y.
TITLE Indications that Live Poultry Markets Are a Major Source of Human
H5N1 Influenza Virus Infection in China
JOURNAL J. Virol. 85 (24), 13432-13438 (2011)
PUBMED 21976646
REFERENCE 2 (bases 1 to 1745)
AUTHORS Lan,Y., Dong,L., Li,Z., Li,X., Zhao,X., Cheng,Y., Tan,m., Yang,L.,
Zou,S., Wen,L., Wang,D., Li,D. and Shu,Y.
TITLE Direct Submission
JOURNAL Submitted (19-SEP-2011) Chinese National Influenza Center, IVDC,
China CDC, 155 Changbai Road, Changping District, Beijing, Beijing,
Beijing 102206, China
FEATURES Location/Qualifiers
source 1..1745
/organism="Influenza A virus (A/Guangxi/1/2009(H5N1))"
/mol_type="viral cRNA"
/strain="A/Guangxi/1/2009"
/serotype="H5N1"
/host="human; gender M; age 18"
/db_xref="taxon:751557"
/segment="4"
/lab_host="E1 passage(s)"
/country="China: Guangxi"
/collection_date="19-Jan-2009"
/note="deceased"
gene 13..1719
/gene="HA"
CDS 13..1719
/gene="HA"
/function="receptor binding and fusion protein"
/codon_start=1
/product="hemagglutinin"
/protein_id="AEO89163.1"
/db_xref="GI:347364489"
/translation="MEKIVLLFAIVSLVKSDHICIGYHANNSTEQVDTIMEKNVTVTH
AQDILEKTHNGKLCDLNGVKPLILKDCSVAGWLLGNPMCDEFIDVPEWSYIVEKANPA
NDLCYPGNFNDYEELKHLLSRINHFEKIQIIPKDSWPDHEASLGVSSACPYQGNSSFF
RNVVWLIKKGNAYPTIKKSYNNTNKEDLLILWGIHHPNDEAEQTRLYQNPTTYISIGT
STLNQRLVPRIATRSKVNGQSGRIDFFWTILKPNDAINFESNGNFIAPEYAYKIVKKG
DSTIMKSEVEYGNCNTRCQTPMGAINSSMPFHNIHPLTIGECPKYVKSNKLVLATGLR
NSPQRERRRRKRGLFGAIAGFIEGGWQGMVDGWYGYHHSNEQGSGYAADKESTQKAID
GVTNKVNSIIDKMNTQFEAVGREFNNLERRIENLNKKMEDGFLDVWTYNAELLVLMEN
ERTLDFHDSNVKNLYDKVRLQLRDNAKELGNGCFEFYHKCDNECMESVRNGTYDYPQY
SEEARLKREEISGVKLESIGTYQILSIYSTVASSLVLAIMVAGLSLWMCSNGSLQCRI
CI"
sig_peptide 13..60
/gene="HA"
mat_peptide 61..1050
/gene="HA"
/product="HA1"
mat_peptide 1051..1716
/gene="HA"
/product="HA2"
ORIGIN
1 caatctgtca aaatggagaa aatagtgctt ctttttgcaa tagtcagcct tgttaaaagc
61 gatcacattt gcattggtta ccatgcaaac aactcgacag agcaggttga cacaataatg
121 gaaaagaacg ttactgttac acatgctcaa gacatactgg aaaagacaca caacgggaag
181 ctctgcgatc taaatggagt gaagcctctg attttaaaag attgtagtgt agcaggatgg
241 ctcctcggga acccaatgtg tgacgaattc atcgatgtgc cagaatggtc ttacatagta
301 gagaaggcca atccagccaa tgacctctgt tacccaggga atttcaacga ttatgaagaa
361 ttgaaacacc tattgagcag aataaaccat tttgagaaaa tacagatcat ccccaaagat
421 tcttggccag atcatgaagc ctcattgggg gtgagctcag catgtccata ccagggaaat
481 tcctcctttt tcagaaatgt ggtatggctt atcaaaaagg gcaatgcata cccaacaata
541 aagaaaagct acaataatac caacaaagaa gatctcttga tactgtgggg gatccaccat
601 cctaatgatg aggcagagca gacaaggctc taccaaaacc caaccaccta tatttccatt
661 gggacatcaa cactaaacca gagattggta ccaagaatag ctactagatc caaagtaaac
721 gggcaaagtg gaaggataga tttcttctgg acaattttaa aaccgaatga tgcaatcaac
781 ttcgagagta atggaaattt cattgctcca gaatatgcat acaaaattgt caagaaagga
841 gactcaacaa ttatgaaaag tgaagtggaa tatggtaact gcaacaccag gtgtcagact
901 ccgatggggg cgattaactc tagtatgcca ttccacaaca tacaccctct caccatcgga
961 gaatgtccca aatatgtgaa atcaaacaaa ttagtccttg cgactgggct cagaaatagt
1021 cctcaaagag agagaagaag aagaaaaaga ggactgtttg gagctatagc aggttttata
1081 gagggaggat ggcagggaat ggtagatggt tggtatgggt accaccacag caatgagcag
1141 gggagtgggt atgctgcaga caaagaatcc actcaaaagg caatagatgg agtcaccaat
1201 aaggtcaact cgatcattga caaaatgaac actcagtttg aagcagtagg aagggaattt
1261 aataacttag agaggagaat agagaattta aacaagaaga tggaagacgg atttctagat
1321 gtctggactt ataatgctga actcctggtt ctcatggaaa atgagagaac tctagacttc
1381 catgactcaa atgtcaagaa cctttacgac aaggtcagac tacagcttag ggataatgca
1441 aaagagctgg gtaacggttg tttcgagttc tatcacaaat gtgataatga atgtatggaa
1501 agtgtaagaa acggaacgta tgactacccg cagtattcag aagaagcaag attaaaaaga
1561 gaggaaataa gtggagtaaa attggaatca ataggaactt accaaatact gtcaatttat
1621 tcaacagtgg cgagttccct agtactggca atcatggttg ctggtctatc tttatggatg
1681 tgttccaacg ggtcgttaca atgcagaatt tgcatttaag tttgtgagtt cagattgtag
1741 ttaaa

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PostPosted: Wed Jan 04, 2012 7:38 am 
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RBD change T192I also in Shenzhen sequence.

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PostPosted: Wed Jan 04, 2012 7:42 am 
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HA nonsynonymous changes (H3 numbering) include
N76D
A87T
N98S
Q119R
S127P
S137A
P140S
I155L
N159D
T163D
K165T
Q173K
T192I
Q196K
P198S
I202V
K216R
S227R
K270R
N279S
R327I
M483I

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PostPosted: Wed Jan 04, 2012 7:46 am 
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R327I (beginning of HA cleavage site)

EPI347304 A/Guangdong-Shenzhen/1/2011(H5N1) (A/H5N1) segment 4 (HA) 27.0 7.412533e+00 14/14 (100%)
EPI337002 A/duck/Zhejiang/2248/2011 (A/H5N1) segment 4 (HA) 27.0 7.412533e+00 14/14 (100%)
EPI337001 A/duck/Zhejiang/2245/2011 (A/H5N1) segment 4 (HA) 27.0 7.412533e+00 14/14 (100%)
EPI337000 A/duck/Zhejiang/2244/2011 (A/H5N1) segment 4 (HA) 27.0 7.412533e+00 14/14 (100%)
EPI336999 A/duck/Zhejiang/2243/2011 (A/H5N1) segment 4 (HA) 27.0 7.412533e+00 14/14 (100%)
EPI336998 A/duck/Zhejiang/2242/2011 (A/H5N1) segment 4 (HA) 27.0 7.412533e+00 14/14 (100%)
EPI336997 A/duck/Zhejiang/224/2011 (A/H5N1) segment 4 (HA) 27.0 7.412533e+00 14/14 (100%)
EPI336996 A/duck/Zhejiang/213/2011 (A/H5N1) segment 4 (HA) 27.0 7.412533e+00 14/14 (100%)
EPI330995 A/duck/Vietnam/NCVD-672/2011 (A/H5N1) segment 4 (HA) 27.0 7.412533e+00 14/14 (100%)
EPI254280 A/oriental magpie robin/Hong Kong/9298/2009 (A/H5N1) segment 4 (HA) 27.0 7.412533e+00 14/14 (100%)
EPI254278 A/feral pigeon/Hong Kong/3409/2009 (A/H5N1) segment 4 (HA) 27.0 7.412533e+00 14/14 (100%)

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PostPosted: Wed Jan 04, 2012 7:48 am 
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niman wrote:
HA nonsynonymous changes (H3 numbering) include
N76D
A87T
N98S
Q119R
S127P
S137A
P140S
I155L
N159D
T163D
K165T
Q173K
T192I
Q196K
P198S
I202V
K216R
S227R
K270R
N279S
R327I
M483I

Large number of HA chnages likely leads to vaccine resistance.

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PostPosted: Wed Jan 04, 2012 8:08 am 
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niman wrote:
RBD change T192I also in Shenzhen sequence.

http://www.recombinomics.com/News/11090 ... angxi.html
Shangxi H5N1 Has Multiple Receptor Binding Domain Changes
Recombinomics Commentary
November 9, 2006

The complete sequence of all eight gene segments from a chicken isolate from northern China, A/chicken/Shangxi/2/2006(H5N1). The release of this sequence may be linked to the comments in lass week's PNAS paper regarding the spread of the Fujian strain of H5N1 in southern China. Researchers from Harbin noted that H5N1 in northern China was quite distance from the southern China isolates, and the above sequence, from the Harbin labs, is quite distance, but is a recombinant with regions of identity with a sequence from northern China, A/chicken/Hebei/326/2005 as well as sequences from southern China, A/chicken/Hunan/2246/2006(H5N1) and A/chicken/Hunan/2292/2006(H5N1)........

However, the isolate from Shangxi had a number of changes in and around the receptor binding domain. The Shangxi sequence had two changes, R220K and K222Q, near the four changes in the Shantou isolates, (V214M, K222R, V223I, S227R) and has four changes flanking the 190 position (A188E, A189T, T192I, L194I). The two related sequences from Hunan also have two of the four changes downstream from 190 (T192I and L194L), but also has two changes upstream, D187N and A189E. Thus, there are five polymorphisms flanking 190 at positions 187, 188, 189, 192, 194 as well as upstream changes at 214, 222, 223, 227 including three versions of 189 and 227. This large number of co-circulating changes in or near the receptor binding domain offers and increasing large number of combinations generated via recombination, which is also happening in the HA cleavage site........

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PostPosted: Wed Jan 04, 2012 9:13 am 
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Commentary

http://www.recombinomics.com/News/01041 ... ation.html

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PostPosted: Wed Jan 04, 2012 10:29 am 
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A715C (S227R)

EPI347304 A/Guangdong-Shenzhen/1/2011(H5N1) (A/H5N1) segment 4 (HA) 27.0 7.414894e+00 14/14 (100%)
EPI335228 A/duck/Lao/6/2010 (A/H5N1) segment 4 (HA) 27.0 7.414894e+00 14/14 (100%)
EPI335212 A/duck/Lao/9/2010 (A/H5N1) segment 4 (HA) 27.0 7.414894e+00 14/14 (100%)
EPI328886 A/duck/Eastern China/108/2008 (A/H5N1) segment 4 (HA) 27.0 7.414894e+00 14/14 (100%)
EPI328878 A/duck/Eastern China/031/2009 (A/H5N5) segment 4 (HA) 27.0 7.414894e+00 14/14 (100%)
EPI328870 A/duck/Eastern China/008/2008 (A/H5N5) segment 4 (HA) 27.0 7.414894e+00 14/14 (100%)

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