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. 2014 Dec;88(23):13897-909.
doi: 10.1128/JVI.01887-14. Epub 2014 Sep 10.

Identification of molecular markers associated with alteration of receptor-binding specificity in a novel genotype of highly pathogenic avian influenza A(H5N1) viruses detected in Cambodia in 2013

Sareth Rith  1 , C Todd Davis  2 , Veasna Duong  1 , Borann Sar  3 , Srey Viseth Horm  1 , Savuth Chin  4 , Sovann Ly  5 , Denis Laurent  6 , Beat Richner  6 , Ikwo Oboho  7 , Yunho Jang  2 , William Davis  2 , Sharmi Thor  2 , Amanda Balish  2 , A Danielle Iuliano  2 , San Sorn  8 , Davun Holl  8 , Touch Sok  5 , Heng Seng  5 , Arnaud Tarantola  1 , Reiko Tsuyuoka  9 , Amy Parry  9 , Nora Chea  9 , Lotfi Allal  10 , Paul Kitsutani  3 , Dora Warren  3 , Michael Prouty  11 , Paul Horwood  1 , Marc-Alain Widdowson  2 , Stephen Lindstrom  2 , Julie Villanueva  2 , Ruben Donis  2 , Nancy Cox  2 , Philippe Buchy  12
Affiliations

Identification of molecular markers associated with alteration of receptor-binding specificity in a novel genotype of highly pathogenic avian influenza A(H5N1) viruses detected in Cambodia in 2013

Sareth Rith et al. J Virol. 2014 Dec.

Abstract

Human infections with influenza A(H5N1) virus in Cambodia increased sharply during 2013. Molecular characterization of viruses detected in clinical specimens from human cases revealed the presence of mutations associated with the alteration of receptor-binding specificity (K189R, Q222L) and respiratory droplet transmission in ferrets (N220K with Q222L). Discovery of quasispecies at position 222 (Q/L), in addition to the absence of the mutations in poultry/environmental samples, suggested that the mutations occurred during human infection and did not transmit further.

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Figures

FIG 1
FIG 1
Neighbor-joining phylogenetic tree of the HA genes of clade 1 highly pathogenic avian influenza A(H5N1) viruses constructed in MEGA5. The nearest reassortant WHO candidate vaccine viruses (CVV) for each group of clade 1 are denoted by CVV at the end of the strain name. Viruses collected in 2012-2013 are denoted with an asterisk. Sequences were aligned using MUSCLE, and amino acid differences at branch nodes indicate shared HA1 substitutions relative to the reference strain, A/Vietnam/1203/2004. Mutations to the right of a strain name indicate amino acid changes found only in that individual virus. Underlined amino acid substitutions indicate previously recognized molecular markers and/or markers of note as listed in the H5N1 Genetic Changes Inventory (24). Branches on the tree with HA sequences from human cases are in bold. Bootstraps greater than 50 generated from 1,000 replicates are shown at branch nodes. The scale bar represents the number of nucleotide substitutions per site.
FIG 2
FIG 2
Neighbor-joining phylogenetic tree of the neuraminidase (NA) and internal genes of highly pathogenic avian influenza A(H5N1) viruses constructed in MEGA5. Viruses collected in 2012-2013 are denoted with an asterisk. Sequences were aligned using MUSCLE; amino acid differences at branch nodes indicate substitutions relative to reference strain A/Vietnam/1203/2004 for the NA gene and A/Hubei/1/2010 for the internal genes. Mutations to the right of each strain name indicate amino acid changes found only in that individual virus. Underlined amino acid substitutions indicate previously recognized molecular markers and/or markers of note as listed in the H5N1 Genetic Changes Inventory (24). Branches on the tree with sequences from human cases are in bold. Bootstraps greater than 50 generated from 1,000 replicates are shown at branch nodes. The scale bar represents the number of nucleotide substitutions per site.
FIG 2
FIG 2
Neighbor-joining phylogenetic tree of the neuraminidase (NA) and internal genes of highly pathogenic avian influenza A(H5N1) viruses constructed in MEGA5. Viruses collected in 2012-2013 are denoted with an asterisk. Sequences were aligned using MUSCLE; amino acid differences at branch nodes indicate substitutions relative to reference strain A/Vietnam/1203/2004 for the NA gene and A/Hubei/1/2010 for the internal genes. Mutations to the right of each strain name indicate amino acid changes found only in that individual virus. Underlined amino acid substitutions indicate previously recognized molecular markers and/or markers of note as listed in the H5N1 Genetic Changes Inventory (24). Branches on the tree with sequences from human cases are in bold. Bootstraps greater than 50 generated from 1,000 replicates are shown at branch nodes. The scale bar represents the number of nucleotide substitutions per site.
FIG 2
FIG 2
Neighbor-joining phylogenetic tree of the neuraminidase (NA) and internal genes of highly pathogenic avian influenza A(H5N1) viruses constructed in MEGA5. Viruses collected in 2012-2013 are denoted with an asterisk. Sequences were aligned using MUSCLE; amino acid differences at branch nodes indicate substitutions relative to reference strain A/Vietnam/1203/2004 for the NA gene and A/Hubei/1/2010 for the internal genes. Mutations to the right of each strain name indicate amino acid changes found only in that individual virus. Underlined amino acid substitutions indicate previously recognized molecular markers and/or markers of note as listed in the H5N1 Genetic Changes Inventory (24). Branches on the tree with sequences from human cases are in bold. Bootstraps greater than 50 generated from 1,000 replicates are shown at branch nodes. The scale bar represents the number of nucleotide substitutions per site.
FIG 2
FIG 2
Neighbor-joining phylogenetic tree of the neuraminidase (NA) and internal genes of highly pathogenic avian influenza A(H5N1) viruses constructed in MEGA5. Viruses collected in 2012-2013 are denoted with an asterisk. Sequences were aligned using MUSCLE; amino acid differences at branch nodes indicate substitutions relative to reference strain A/Vietnam/1203/2004 for the NA gene and A/Hubei/1/2010 for the internal genes. Mutations to the right of each strain name indicate amino acid changes found only in that individual virus. Underlined amino acid substitutions indicate previously recognized molecular markers and/or markers of note as listed in the H5N1 Genetic Changes Inventory (24). Branches on the tree with sequences from human cases are in bold. Bootstraps greater than 50 generated from 1,000 replicates are shown at branch nodes. The scale bar represents the number of nucleotide substitutions per site.
FIG 2
FIG 2
Neighbor-joining phylogenetic tree of the neuraminidase (NA) and internal genes of highly pathogenic avian influenza A(H5N1) viruses constructed in MEGA5. Viruses collected in 2012-2013 are denoted with an asterisk. Sequences were aligned using MUSCLE; amino acid differences at branch nodes indicate substitutions relative to reference strain A/Vietnam/1203/2004 for the NA gene and A/Hubei/1/2010 for the internal genes. Mutations to the right of each strain name indicate amino acid changes found only in that individual virus. Underlined amino acid substitutions indicate previously recognized molecular markers and/or markers of note as listed in the H5N1 Genetic Changes Inventory (24). Branches on the tree with sequences from human cases are in bold. Bootstraps greater than 50 generated from 1,000 replicates are shown at branch nodes. The scale bar represents the number of nucleotide substitutions per site.
FIG 2
FIG 2
Neighbor-joining phylogenetic tree of the neuraminidase (NA) and internal genes of highly pathogenic avian influenza A(H5N1) viruses constructed in MEGA5. Viruses collected in 2012-2013 are denoted with an asterisk. Sequences were aligned using MUSCLE; amino acid differences at branch nodes indicate substitutions relative to reference strain A/Vietnam/1203/2004 for the NA gene and A/Hubei/1/2010 for the internal genes. Mutations to the right of each strain name indicate amino acid changes found only in that individual virus. Underlined amino acid substitutions indicate previously recognized molecular markers and/or markers of note as listed in the H5N1 Genetic Changes Inventory (24). Branches on the tree with sequences from human cases are in bold. Bootstraps greater than 50 generated from 1,000 replicates are shown at branch nodes. The scale bar represents the number of nucleotide substitutions per site.
FIG 2
FIG 2
Neighbor-joining phylogenetic tree of the neuraminidase (NA) and internal genes of highly pathogenic avian influenza A(H5N1) viruses constructed in MEGA5. Viruses collected in 2012-2013 are denoted with an asterisk. Sequences were aligned using MUSCLE; amino acid differences at branch nodes indicate substitutions relative to reference strain A/Vietnam/1203/2004 for the NA gene and A/Hubei/1/2010 for the internal genes. Mutations to the right of each strain name indicate amino acid changes found only in that individual virus. Underlined amino acid substitutions indicate previously recognized molecular markers and/or markers of note as listed in the H5N1 Genetic Changes Inventory (24). Branches on the tree with sequences from human cases are in bold. Bootstraps greater than 50 generated from 1,000 replicates are shown at branch nodes. The scale bar represents the number of nucleotide substitutions per site.
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References

    1. Gao R, Cao B, Hu Y, Feng Z, Wang D, Hu W, Chen J, Jie Z, Qiu H, Xu K, Xu X, Lu H, Zhu W, Gao Z, Xiang N, Shen Y, He Z, Gu Y, Zhang Z, Yang Y, Zhao X, Zhou L, Li X, Zou S, Zhang Y, Li X, Yang L, Guo J, Dong J, Li Q, Dong L, Zhu Y, Bai T, Wang S, Hao P, Yang W, Zhang Y, Han J, Yu H, Li D, Gao GF, Wu G, Wang Y, Yuan Z, Shu Y. 2013. Human infection with a novel avian-origin influenza A (H7N9) virus. N. Engl. J. Med. 368:1888–1897. 10.1056/NEJMoa1304459. - DOI - PubMed
    1. Russell CA, Fonville JM, Brown AEX, Burke DF, Smith DL, James SL, Herfst S, van Boheemen S, Linster M, Schrauwen EJ, Katzelnick L, Mosterín A, Kuiken T, Maher E, Neumann G, Osterhaus AD, Kawaoka Y, Fouchier RA, Smith DJ. 2012. The potential for respiratory droplet-transmissible A/H5N1 influenza virus to evolve in a mammalian host. Science 336:1541–1547. 10.1126/science.1222526. - DOI - PMC - PubMed
    1. Stevens J, Blixt O, Chen L-M, Donis RO, Paulson JC, Wilson IA. 2008. Recent avian H5N1 viruses exhibit increased propensity for acquiring human receptor specificity. J. Mol. Biol. 381:1382–1394. 10.1016/j.jmb.2008.04.016. - DOI - PMC - PubMed
    1. Stevens J, Blixt O, Tumpey TM, Taubenberger JK, Paulson JC, Wilson IA. 2006. Structure and receptor specificity of the hemagglutinin from an H5N1 influenza virus. Science 312:404–410. 10.1126/science.1124513. - DOI - PubMed
    1. Chutinimitkul S, van Riel D, Munster VJ, van den Brand JMA, Rimmelzwaan GF, Kuiken T, Osterhaus AD, Fouchier RA, de Wit E. 2010. In vitro assessment of attachment pattern and replication efficiency of H5N1 influenza A viruses with altered receptor specificity. J. Virol. 84:6825–6833. 10.1128/JVI.02737-09. - DOI - PMC - PubMed

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