Rhiza Labs FluTracker Forum

Institut Pasteur in Cambodia has released a series of recent sequences on human H5N1 cases in Cambodia, including A/Cambodia/V0606311/2011 collected June 6, 2011, which has the receptor binding domain change S227N.

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S227N was in first reported H5N1 Qinghai (clade 2,2) human case (in Turkey in late 2005).

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LOCUS AEN68938 568 aa linear VRL 01-NOV-2011
DEFINITION hemagglutinin [Influenza A virus (A/Cambodia/V0606311/2011(H5N1))].
ACCESSION AEN68938
VERSION AEN68938.1 GI:345098975
DBSOURCE accession JN588809.1
KEYWORDS .
SOURCE Influenza A virus (A/Cambodia/V0606311/2011(H5N1))
ORGANISM Influenza A virus (A/Cambodia/V0606311/2011(H5N1))
Viruses; ssRNA negative-strand viruses; Orthomyxoviridae;
Influenzavirus A.
REFERENCE 1 (residues 1 to 568)
AUTHORS Buchy,P. and Mardy,S.
TITLE Direct Submission
JOURNAL Submitted (16-AUG-2011) Virology Unit, Institut Pasteur in
Cambodia, 5 Monivong Blvd, BP 983, Phnom Penh BP 983, Cambodia
COMMENT Method: conceptual translation.
FEATURES Location/Qualifiers
source 1..568
/organism="Influenza A virus
(A/Cambodia/V0606311/2011(H5N1))"
/strain="A/Cambodia/V0606311/2011"
/serotype="H5N1"
/host="Homo sapiens"
/db_xref="taxon:1076957"
/segment="4"
/country="Cambodia: Prey Veng"
/collection_date="06-Jun-2011"
Protein 1..568
/product="hemagglutinin"
CDS 1..568
/gene="HA"
/coded_by="JN588809.1:10..1716"
ORIGIN
1 mekivllfvi vnlvksdqic igyhannste qvdtimeknv tvthaqdile kthngklcdl
61 dgirplilrd csvagwllgn pmcdefinvp ewsyivekan pvndicypgv fndyeelkhl
121 lsrinhfekv qiipksswps heaslgvsaa cpyqgkssff rnvvwlikkn styptikrsy
181 nntgqedlli mwgihhpnda aeqtklyqnp ttyisvgtst lnqrltpria trskvngqng
241 rmeffwtilk pndainfesn gnfiapeyay kivkkgdsti mkseleygnc ntrcqtpmga
301 inssmpfhni hpltigecpk yvksnrlvla tglrnspqre grrkkrglfg aiagfieggw
361 qgmvdgwygy hhsneqgsgy aadkestqka idgvtnkvns iidkmntqfe avgrefnnle
421 rrienlnkkm edgfldvwty naellvlmen ertldfhdsn vknlydkvrl qlrdnakelg
481 ngcfefyhkc dnecmesvrn gtydypqyse earlkreeis gvklesigvy qilsiystva
541 sslalaimva glslwmcsng slqcrici

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In vitro evolution of H5N1 avian influenza virus toward human-type receptor specificityLi-Mei Chena, 1, Ola Blixtb, d, 1, 2, James Stevensa, c, Aleksandr S. Lipatova, Charles T. Davisa, Brian E. Collinsb, d, Nancy J. Coxa, James C. Paulsonb, d, 1, Ruben O. Donisa, , 1,

Purchase a Influenza Division, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333, United States
b Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, United States
c Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, United States
d Glycan Array Synthesis Core-D, Consortium for Functional Glycomics, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, United States
Received 27 August 2011; revised 26 September 2011; Accepted 10 October 2011. Available online 5 November 2011.


Abstract
Acquisition of α2-6 sialoside receptor specificity by α2-3 specific highly-pathogenic avian influenza viruses (H5N1) is thought to be a prerequisite for efficient transmission in humans. By in vitro selection for binding α2-6 sialosides, we identified four variant viruses with amino acid substitutions in the hemagglutinin (S227N, D187G, E190G, and Q196R) that revealed modestly increased α2-6 and minimally decreased α2-3 binding by glycan array analysis. However, a mutant virus combining Q196R with mutations from previous pandemic viruses (Q226L and G228S) revealed predominantly α2-6 binding. Unlike the wild type H5N1, this mutant virus was transmitted by direct contact in the ferret model although not by airborne respiratory droplets. However, a reassortant virus with the mutant hemagglutinin, a human N2 neuraminidase and internal genes from an H5N1 virus was partially transmitted via respiratory droplets. The complex changes required for airborne transmissibility in ferrets suggest that extensive evolution is needed for H5N1 transmissibility in humans.

Keywords: Highly pathogenic avian influenza virus; Hemagglutinin; Host cell receptor; Virus attachment; H5N1; Sialoglycan; Host range; Pandemic virus emergence

http://www.sciencedirect.com/science/ar ... 2211004752

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S227N at GISAID

EPI341364 A/Cambodia/V0606311/2011 (A/H5N1) segment 4 (HA) 27.0 7.217420e+00 14/14 (100%)
EPI255349 A/Egypt/10217-NAMRU3/2007 (A/H5N1) segment 4 (HA) 27.0 7.217420e+00 14/14 (100%)
EPI165070 A/Egypt/2546-NAMRU3/2008 (A/H5N1) segment 4 (HA) 27.0 7.217420e+00 14/14 (100%)
EPI118835 A/Turkey/65596/2006 (A/H5N1) segment 4 (HA) 27.0 7.217420e+00 14/14 (100%)
EPI118798 A/Turkey/12/2006 (A/H5N1) segment 4 (HA) 27.0 7.217420e+00 14/14 (100%)
EPI116501 A/Hong Kong/213/2003 (A/H5N1) segment 4 (HA) 27.0 7.217420e+00 14/14 (100%)
EPI110237 A/Egypt/2947-NAMRU3/2006 (A/H5N1) segment 4 (HA) 27.0 7.217420e+00 14/14 (100%)
EPI20508 A/Hong Kong/213/03 (A/H5N1) segment 4 (HA) 27.0 7.217420e+00 14/14 (100%)
EPI20506 A/HK/212/03 (A/H5N1) segment 4 (HA) 27.0 7.217420e+00 14/14 (100%)
EPI1161 A/Hong Kong/213/03 (A/H5N1) segment 4 (HA) 27.0 7.217420e+00 14/14 (100%)

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