Nationwide Molecular Surveillance of Pandemic H1N1 Influenza A Virus Genomes: Canada, 2009
Identifieur interne : 000805 ( Pmc/Checkpoint ); précédent : 000804; suivant : 000806Nationwide Molecular Surveillance of Pandemic H1N1 Influenza A Virus Genomes: Canada, 2009
Auteurs : Morag Graham [Canada] ; Binhua Liang [Canada] ; Gary Van Domselaar [Canada] ; Nathalie Bastien [Canada] ; Carole Beaudoin [Canada] ; Shaun Tyler [Canada] ; Brynn Kaplen [Canada] ; Erika Landry [Canada] ; Yan Li [Canada]Source :
- PLoS ONE [ 1932-6203 ] ; 2011.
Abstract
In April 2009, a novel triple-reassortant swine influenza A H1N1 virus (“A/H1N1pdm”; also known as SOIV) was detected and spread globally as the first influenza pandemic of the 21st century. Sequencing has since been conducted at an unprecedented rate globally in order to monitor the diversification of this emergent virus and to track mutations that may affect virus behavior.
By Sanger sequencing, we determined consensus whole-genome sequences for A/H1N1pdm viruses sampled nationwide in Canada over 33 weeks during the 2009 first and second pandemic waves. A total of 235 virus genomes sampled from unique subjects were analyzed, providing insight into the temporal and spatial trajectory of A/H1N1pdm lineages within Canada. Three clades (2, 3, and 7) were identifiable within the first two weeks of A/H1N1pdm appearance, with clades 5 and 6 appearing thereafter; further diversification was not apparent. Only two viral sites displayed evidence of adaptive evolution, located in hemagglutinin (HA) corresponding to D222 in the HA receptor-binding site, and to E374 at HA2-subunit position 47. Among the Canadian sampled viruses, we observed notable genetic diversity (1.47×10−3 amino acid substitutions per site) in the gene encoding PB1, particularly within the viral genomic RNA (vRNA)-binding domain (residues 493–757). This genome data set supports the conclusion that A/H1N1pdm is evolving but not excessively relative to other H1N1 influenza A viruses. Entropy analysis was used to investigate whether any mutated A/H1N1pdm protein residues were associated with infection severity; however no virus genotypes were observed to trend with infection severity. One virus that harboured heterozygote coding mutations, including PB2 D567D/G, was attributed to a severe and potentially mixed infection; yet the functional significance of this PB2 mutation remains unknown.
These findings contribute to enhanced understanding of Influenza A/H1N1pdm viral dynamics.
Url:
DOI: 10.1371/journal.pone.0016087
PubMed: 21249207
PubMed Central: 3017559
Affiliations:
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wicri:level="4"><nlm:aff id="aff2"><addr-line>Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba</wicri:regionArea><orgName type="university">Université du Manitoba</orgName><placeName><settlement type="city">Winnipeg</settlement><region type="state">Manitoba</region></placeName></affiliation></author><author><name sortKey="Liang, Binhua" sort="Liang, Binhua" uniqKey="Liang B" first="Binhua" last="Liang">Binhua Liang</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba</wicri:regionArea><wicri:noRegion>Manitoba</wicri:noRegion></affiliation></author><author><name sortKey="Van Domselaar, Gary" sort="Van Domselaar, Gary" uniqKey="Van Domselaar G" first="Gary" last="Van Domselaar">Gary Van Domselaar</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba</wicri:regionArea><wicri:noRegion>Manitoba</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="aff2"><addr-line>Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba</wicri:regionArea><orgName type="university">Université du Manitoba</orgName><placeName><settlement type="city">Winnipeg</settlement><region type="state">Manitoba</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff3"><addr-line>Department of Computer Science, University of Manitoba, Winnipeg, Manitoba, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Computer Science, University of Manitoba, Winnipeg, Manitoba</wicri:regionArea><orgName type="university">Université du Manitoba</orgName><placeName><settlement type="city">Winnipeg</settlement><region type="state">Manitoba</region></placeName></affiliation></author><author><name sortKey="Bastien, Nathalie" sort="Bastien, Nathalie" uniqKey="Bastien N" first="Nathalie" last="Bastien">Nathalie Bastien</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba</wicri:regionArea><wicri:noRegion>Manitoba</wicri:noRegion></affiliation></author><author><name sortKey="Beaudoin, Carole" sort="Beaudoin, Carole" uniqKey="Beaudoin C" first="Carole" last="Beaudoin">Carole Beaudoin</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba</wicri:regionArea><wicri:noRegion>Manitoba</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="aff4"><addr-line>Department of Community Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Community Health Sciences, University of Manitoba, Winnipeg, Manitoba</wicri:regionArea><orgName type="university">Université du Manitoba</orgName><placeName><settlement type="city">Winnipeg</settlement><region type="state">Manitoba</region></placeName></affiliation></author><author><name sortKey="Tyler, Shaun" sort="Tyler, Shaun" uniqKey="Tyler S" first="Shaun" last="Tyler">Shaun Tyler</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba</wicri:regionArea><wicri:noRegion>Manitoba</wicri:noRegion></affiliation></author><author><name sortKey="Kaplen, Brynn" sort="Kaplen, Brynn" uniqKey="Kaplen B" first="Brynn" last="Kaplen">Brynn Kaplen</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba</wicri:regionArea><wicri:noRegion>Manitoba</wicri:noRegion></affiliation></author><author><name sortKey="Landry, Erika" sort="Landry, Erika" uniqKey="Landry E" first="Erika" last="Landry">Erika Landry</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba</wicri:regionArea><wicri:noRegion>Manitoba</wicri:noRegion></affiliation></author><author><name sortKey="Li, Yan" sort="Li, Yan" uniqKey="Li Y" first="Yan" last="Li">Yan Li</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba</wicri:regionArea><wicri:noRegion>Manitoba</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="aff2"><addr-line>Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba</wicri:regionArea><orgName type="university">Université du Manitoba</orgName><placeName><settlement type="city">Winnipeg</settlement><region type="state">Manitoba</region></placeName></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>In April 2009, a novel triple-reassortant swine influenza A H1N1 virus (“A/H1N1pdm”; also known as SOIV) was detected and spread globally as the first influenza pandemic of the 21<sup>st</sup> century. Sequencing has since been conducted at an unprecedented rate globally in order to monitor the diversification of this emergent virus and to track mutations that may affect virus behavior.</p></sec><sec><title>Methodology/Principal Findings</title><p>By Sanger sequencing, we determined consensus whole-genome sequences for A/H1N1pdm viruses sampled nationwide in Canada over 33 weeks during the 2009 first and second pandemic waves. A total of 235 virus genomes sampled from unique subjects were analyzed, providing insight into the temporal and spatial trajectory of A/H1N1pdm lineages within Canada. Three clades (2, 3, and 7) were identifiable within the first two weeks of A/H1N1pdm appearance, with clades 5 and 6 appearing thereafter; further diversification was not apparent. Only two viral sites displayed evidence of adaptive evolution, located in hemagglutinin (HA) corresponding to D222 in the HA receptor-binding site, and to E374 at HA2-subunit position 47. Among the Canadian sampled viruses, we observed notable genetic diversity (1.47×10<sup>−3</sup> amino acid substitutions per site) in the gene encoding PB1, particularly within the viral genomic RNA (vRNA)-binding domain (residues 493–757). This genome data set supports the conclusion that A/H1N1pdm is evolving but not excessively relative to other H1N1 influenza A viruses. Entropy analysis was used to investigate whether any mutated A/H1N1pdm protein residues were associated with infection severity; however no virus genotypes were observed to trend with infection severity. One virus that harboured heterozygote coding mutations, including PB2 D567D/G, was attributed to a severe and potentially mixed infection; yet the functional significance of this PB2 mutation remains unknown.</p></sec><sec><title>Conclusions/Significance</title><p>These findings contribute to enhanced understanding of Influenza A/H1N1pdm viral dynamics.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Webster, Rg" uniqKey="Webster R">RG Webster</name></author><author><name sortKey="Bean, Wj" uniqKey="Bean W">WJ Bean</name></author><author><name sortKey="Gorman, Ot" uniqKey="Gorman O">OT Gorman</name></author><author><name sortKey="Chambers, Tm" uniqKey="Chambers T">TM Chambers</name></author><author><name sortKey="Kawaoka, Y" uniqKey="Kawaoka Y">Y Kawaoka</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rambaut, A" uniqKey="Rambaut A">A Rambaut</name></author><author><name sortKey="Pybus, Og" uniqKey="Pybus O">OG Pybus</name></author><author><name sortKey="Nelson, Mi" uniqKey="Nelson M">MI Nelson</name></author><author><name sortKey="Viboud, C" uniqKey="Viboud C">C Viboud</name></author><author><name sortKey="Taubenberger, Jk" uniqKey="Taubenberger J">JK Taubenberger</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Domingo, E" uniqKey="Domingo E">E Domingo</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Bautista, E" uniqKey="Bautista E">E Bautista</name></author><author><name sortKey="Chotpitayasunondh, T" uniqKey="Chotpitayasunondh T">T Chotpitayasunondh</name></author><author><name sortKey="Gao, Z" uniqKey="Gao Z">Z Gao</name></author><author><name sortKey="Harper, Sa" uniqKey="Harper S">SA Harper</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Garten, Rj" uniqKey="Garten R">RJ Garten</name></author><author><name sortKey="Davis, Ct" uniqKey="Davis C">CT Davis</name></author><author><name sortKey="Russell, Ca" uniqKey="Russell C">CA Russell</name></author><author><name sortKey="Shu, B" uniqKey="Shu B">B Shu</name></author><author><name sortKey="Lindstrom, S" uniqKey="Lindstrom S">S Lindstrom</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cutler, J" uniqKey="Cutler J">J Cutler</name></author><author><name sortKey="Schleihauf, E" uniqKey="Schleihauf E">E Schleihauf</name></author><author><name sortKey="Hatchette, Tf" uniqKey="Hatchette T">TF Hatchette</name></author><author><name sortKey="Billard, B" uniqKey="Billard B">B Billard</name></author><author><name sortKey="Watson Creed, G" uniqKey="Watson Creed G">G Watson-Creed</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nelson, M" uniqKey="Nelson M">M Nelson</name></author><author><name sortKey="Spiro, D" uniqKey="Spiro D">D Spiro</name></author><author><name sortKey="Wentworth, D" uniqKey="Wentworth D">D Wentworth</name></author><author><name sortKey="Beck, E" uniqKey="Beck E">E Beck</name></author><author><name sortKey="Fan, J" uniqKey="Fan J">J Fan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jombart, T" uniqKey="Jombart T">T Jombart</name></author><author><name sortKey="Eggo, Rm" uniqKey="Eggo R">RM Eggo</name></author><author><name sortKey="Dodd, Pj" uniqKey="Dodd P">PJ Dodd</name></author><author><name sortKey="Balloux, F" uniqKey="Balloux F">F Balloux</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Igarashi, M" uniqKey="Igarashi M">M Igarashi</name></author><author><name sortKey="Ito, K" uniqKey="Ito K">K Ito</name></author><author><name sortKey="Yoshida, R" uniqKey="Yoshida R">R Yoshida</name></author><author><name sortKey="Tomabechi, D" uniqKey="Tomabechi D">D Tomabechi</name></author><author><name sortKey="Kida, H" uniqKey="Kida H">H Kida</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yang, H" uniqKey="Yang H">H Yang</name></author><author><name sortKey="Carney, P" uniqKey="Carney P">P Carney</name></author><author><name sortKey="Stevens, J" uniqKey="Stevens J">J Stevens</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Munk, K" uniqKey="Munk K">K Munk</name></author><author><name sortKey="Pritzer, E" uniqKey="Pritzer E">E Pritzer</name></author><author><name sortKey="Kretzschmar, E" uniqKey="Kretzschmar E">E Kretzschmar</name></author><author><name sortKey="Gutte, B" uniqKey="Gutte B">B Gutte</name></author><author><name sortKey="Garten, W" uniqKey="Garten W">W Garten</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Stevens, J" uniqKey="Stevens J">J Stevens</name></author><author><name sortKey="Blixt, O" uniqKey="Blixt O">O Blixt</name></author><author><name sortKey="Glaser, L" uniqKey="Glaser L">L Glaser</name></author><author><name sortKey="Taubenberger, Jk" uniqKey="Taubenberger J">JK Taubenberger</name></author><author><name sortKey="Palese, P" uniqKey="Palese P">P Palese</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Maurer Stroh, S" uniqKey="Maurer Stroh S">S Maurer-Stroh</name></author><author><name sortKey="Lee, Rt" uniqKey="Lee R">RT Lee</name></author><author><name sortKey="Eisenhaber, F" uniqKey="Eisenhaber F">F Eisenhaber</name></author><author><name sortKey="Cui, L" uniqKey="Cui L">L Cui</name></author><author><name sortKey="Phuah, Sp" uniqKey="Phuah S">SP Phuah</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ekiert, Dc" uniqKey="Ekiert D">DC Ekiert</name></author><author><name sortKey="Bhabha, G" uniqKey="Bhabha G">G Bhabha</name></author><author><name sortKey="Elsliger, Ma" uniqKey="Elsliger M">MA Elsliger</name></author><author><name sortKey="Friesen, Rh" uniqKey="Friesen R">RH Friesen</name></author><author><name sortKey="Jongeneelen, M" uniqKey="Jongeneelen M">M Jongeneelen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Maurer Stroh, S" uniqKey="Maurer Stroh S">S Maurer-Stroh</name></author><author><name sortKey="Ma, J" uniqKey="Ma J">J Ma</name></author><author><name sortKey="Lee, Rt" uniqKey="Lee R">RT Lee</name></author><author><name sortKey="Sirota, Fl" uniqKey="Sirota F">FL Sirota</name></author><author><name sortKey="Eisenhaber, F" uniqKey="Eisenhaber F">F Eisenhaber</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ruigrok, Rw" uniqKey="Ruigrok R">RW Ruigrok</name></author><author><name sortKey="Crepin, T" uniqKey="Crepin T">T Crepin</name></author><author><name sortKey="Hart, Dj" uniqKey="Hart D">DJ Hart</name></author><author><name sortKey="Cusack, S" uniqKey="Cusack S">S Cusack</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nelson, Mi" uniqKey="Nelson M">MI Nelson</name></author><author><name sortKey="Simonsen, L" uniqKey="Simonsen L">L Simonsen</name></author><author><name sortKey="Viboud, C" uniqKey="Viboud C">C Viboud</name></author><author><name sortKey="Miller, Ma" uniqKey="Miller M">MA Miller</name></author><author><name sortKey="Taylor, J" uniqKey="Taylor J">J Taylor</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shen, J" uniqKey="Shen J">J Shen</name></author><author><name sortKey="Ma, J" uniqKey="Ma J">J Ma</name></author><author><name sortKey="Wang, Q" uniqKey="Wang Q">Q Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Barman, S" uniqKey="Barman S">S Barman</name></author><author><name sortKey="Nayak, Dp" uniqKey="Nayak D">DP Nayak</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Baudin, F" uniqKey="Baudin F">F Baudin</name></author><author><name sortKey="Petit, I" uniqKey="Petit I">I Petit</name></author><author><name sortKey="Weissenhorn, W" uniqKey="Weissenhorn W">W Weissenhorn</name></author><author><name sortKey="Ruigrok, Rw" uniqKey="Ruigrok R">RW Ruigrok</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Furuse, Y" uniqKey="Furuse Y">Y Furuse</name></author><author><name sortKey="Suzuki, A" uniqKey="Suzuki A">A Suzuki</name></author><author><name sortKey="Kamigaki, T" uniqKey="Kamigaki T">T Kamigaki</name></author><author><name sortKey="Oshitani, H" uniqKey="Oshitani H">H Oshitani</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tarendeau, F" uniqKey="Tarendeau F">F Tarendeau</name></author><author><name sortKey="Crepin, T" uniqKey="Crepin T">T Crepin</name></author><author><name sortKey="Guilligay, D" uniqKey="Guilligay D">D Guilligay</name></author><author><name sortKey="Ruigrok, Rw" uniqKey="Ruigrok R">RW Ruigrok</name></author><author><name sortKey="Cusack, S" uniqKey="Cusack S">S Cusack</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Miotto, O" uniqKey="Miotto O">O Miotto</name></author><author><name sortKey="Heiny, At" uniqKey="Heiny A">AT Heiny</name></author><author><name sortKey="Albrecht, R" uniqKey="Albrecht R">R Albrecht</name></author><author><name sortKey="Garcia Sastre, A" uniqKey="Garcia Sastre A">A Garcia-Sastre</name></author><author><name sortKey="Tan, Tw" uniqKey="Tan T">TW Tan</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Embree, J" uniqKey="Embree J">J Embree</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kumar, A" uniqKey="Kumar A">A Kumar</name></author><author><name sortKey="Zarychanski, R" uniqKey="Zarychanski R">R Zarychanski</name></author><author><name sortKey="Pinto, R" uniqKey="Pinto R">R Pinto</name></author><author><name sortKey="Cook, Dj" uniqKey="Cook D">DJ Cook</name></author><author><name sortKey="Marshall, J" uniqKey="Marshall J">J Marshall</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lin, D" uniqKey="Lin D">D Lin</name></author><author><name sortKey="Lan, J" uniqKey="Lan J">J Lan</name></author><author><name sortKey="Zhang, Z" uniqKey="Zhang Z">Z Zhang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Das, K" uniqKey="Das K">K Das</name></author><author><name sortKey="Aramini, Jm" uniqKey="Aramini J">JM Aramini</name></author><author><name sortKey="Ma, Lc" uniqKey="Ma L">LC Ma</name></author><author><name sortKey="Krug, Rm" uniqKey="Krug R">RM Krug</name></author><author><name sortKey="Arnold, E" uniqKey="Arnold E">E Arnold</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fislova, T" uniqKey="Fislova T">T Fislova</name></author><author><name sortKey="Thomas, B" uniqKey="Thomas B">B Thomas</name></author><author><name sortKey="Graef, Km" uniqKey="Graef K">KM Graef</name></author><author><name sortKey="Fodor, E" uniqKey="Fodor E">E Fodor</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Furuse, Y" uniqKey="Furuse Y">Y Furuse</name></author><author><name sortKey="Shimabukuro, K" uniqKey="Shimabukuro K">K Shimabukuro</name></author><author><name sortKey="Odagiri, T" uniqKey="Odagiri T">T Odagiri</name></author><author><name sortKey="Sawayama, R" uniqKey="Sawayama R">R Sawayama</name></author><author><name sortKey="Okada, T" uniqKey="Okada T">T Okada</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Greenbaum, Ja" uniqKey="Greenbaum J">JA Greenbaum</name></author><author><name sortKey="Kotturi, Mf" uniqKey="Kotturi M">MF Kotturi</name></author><author><name sortKey="Kim, Y" uniqKey="Kim Y">Y Kim</name></author><author><name sortKey="Oseroff, C" uniqKey="Oseroff C">C Oseroff</name></author><author><name sortKey="Vaughan, K" uniqKey="Vaughan K">K Vaughan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Smith, Gj" uniqKey="Smith G">GJ Smith</name></author><author><name sortKey="Vijaykrishna, D" uniqKey="Vijaykrishna D">D Vijaykrishna</name></author><author><name sortKey="Bahl, J" uniqKey="Bahl J">J Bahl</name></author><author><name sortKey="Lycett, Sj" uniqKey="Lycett S">SJ Lycett</name></author><author><name sortKey="Worobey, M" uniqKey="Worobey M">M Worobey</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Akarsu, H" uniqKey="Akarsu H">H Akarsu</name></author><author><name sortKey="Boulo, S" uniqKey="Boulo S">S Boulo</name></author><author><name sortKey="Ruigrok, Rwh" uniqKey="Ruigrok R">RWH Ruigrok</name></author><author><name sortKey="Baudin, F" uniqKey="Baudin F">F Baudin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gabriel, G" uniqKey="Gabriel G">G Gabriel</name></author><author><name sortKey="Herwig, A" uniqKey="Herwig A">A Herwig</name></author><author><name sortKey="Klenk, Hd" uniqKey="Klenk H">HD Klenk</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Naffakh, N" uniqKey="Naffakh N">N Naffakh</name></author><author><name sortKey="Tomoiu, A" uniqKey="Tomoiu A">A Tomoiu</name></author><author><name sortKey="Rameix Welti, Ma" uniqKey="Rameix Welti M">MA Rameix-Welti</name></author><author><name sortKey="Van Der Werf, S" uniqKey="Van Der Werf S">S van der Werf</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, Ot" uniqKey="Li O">OT Li</name></author><author><name sortKey="Chan, Mc" uniqKey="Chan M">MC Chan</name></author><author><name sortKey="Leung, Cs" uniqKey="Leung C">CS Leung</name></author><author><name sortKey="Chan, Rw" uniqKey="Chan R">RW Chan</name></author><author><name sortKey="Guan, Y" uniqKey="Guan Y">Y Guan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mehle, A" uniqKey="Mehle A">A Mehle</name></author><author><name sortKey="Doudna, Ja" uniqKey="Doudna J">JA Doudna</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Olsen, Cw" uniqKey="Olsen C">CW Olsen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tumpey, Tm" uniqKey="Tumpey T">TM Tumpey</name></author><author><name sortKey="Garcia Sastre, A" uniqKey="Garcia Sastre A">A Garcia-Sastre</name></author><author><name sortKey="Taubenberger, Jk" uniqKey="Taubenberger J">JK Taubenberger</name></author><author><name sortKey="Palese, P" uniqKey="Palese P">P Palese</name></author><author><name sortKey="Swayne, De" uniqKey="Swayne D">DE Swayne</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Basler, Cf" uniqKey="Basler C">CF Basler</name></author><author><name sortKey="Aguilar, Pv" uniqKey="Aguilar P">PV Aguilar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Marjuki, H" uniqKey="Marjuki H">H Marjuki</name></author><author><name sortKey="Yen, Hl" uniqKey="Yen H">HL Yen</name></author><author><name sortKey="Franks, J" uniqKey="Franks J">J Franks</name></author><author><name sortKey="Webster, Rg" uniqKey="Webster R">RG Webster</name></author><author><name sortKey="Pleschka, S" uniqKey="Pleschka S">S Pleschka</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kilander, A" uniqKey="Kilander A">A Kilander</name></author><author><name sortKey="Rykkvin, R" uniqKey="Rykkvin R">R Rykkvin</name></author><author><name sortKey="Dudman, Sg" uniqKey="Dudman S">SG Dudman</name></author><author><name sortKey="Hungnes, O" uniqKey="Hungnes O">O Hungnes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Melidou, A" uniqKey="Melidou A">A Melidou</name></author><author><name sortKey="Gioula, G" uniqKey="Gioula G">G Gioula</name></author><author><name sortKey="Exindari, M" uniqKey="Exindari M">M Exindari</name></author><author><name sortKey="Chatzidimitriou, D" uniqKey="Chatzidimitriou D">D Chatzidimitriou</name></author><author><name sortKey="Diza, E" uniqKey="Diza E">E Diza</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Glinsky, Gv" uniqKey="Glinsky G">GV Glinsky</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hamelin, Me" uniqKey="Hamelin M">ME Hamelin</name></author><author><name sortKey="Baz, M" uniqKey="Baz M">M Baz</name></author><author><name sortKey="Abed, Y" uniqKey="Abed Y">Y Abed</name></author><author><name sortKey="Couture, C" uniqKey="Couture C">C Couture</name></author><author><name sortKey="Joubert, P" uniqKey="Joubert P">P Joubert</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nobusawa, E" uniqKey="Nobusawa E">E Nobusawa</name></author><author><name sortKey="Sato, K" uniqKey="Sato K">K Sato</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tumpey, Tm" uniqKey="Tumpey T">TM Tumpey</name></author><author><name sortKey="Maines, Tr" uniqKey="Maines T">TR Maines</name></author><author><name sortKey="Van Hoeven, N" uniqKey="Van Hoeven N">N Van Hoeven</name></author><author><name sortKey="Glaser, L" uniqKey="Glaser L">L Glaser</name></author><author><name sortKey="Solorzano, A" uniqKey="Solorzano A">A Solorzano</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ghedin, E" uniqKey="Ghedin E">E Ghedin</name></author><author><name sortKey="Fitch, A" uniqKey="Fitch A">A Fitch</name></author><author><name sortKey="Boyne, A" uniqKey="Boyne A">A Boyne</name></author><author><name sortKey="Griesemer, S" uniqKey="Griesemer S">S Griesemer</name></author><author><name sortKey="Depasse, J" uniqKey="Depasse J">J DePasse</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Hoffmann, E" uniqKey="Hoffmann E">E Hoffmann</name></author><author><name sortKey="Stech, J" uniqKey="Stech J">J Stech</name></author><author><name sortKey="Guan, Y" uniqKey="Guan Y">Y Guan</name></author><author><name sortKey="Webster, Rg" uniqKey="Webster R">RG Webster</name></author><author><name sortKey="Perez, Dr" uniqKey="Perez D">DR Perez</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Larkin, Ma" uniqKey="Larkin M">MA Larkin</name></author><author><name sortKey="Blackshields, G" uniqKey="Blackshields G">G Blackshields</name></author><author><name sortKey="Brown, Np" uniqKey="Brown N">NP Brown</name></author><author><name sortKey="Chenna, R" uniqKey="Chenna R">R Chenna</name></author><author><name sortKey="Mcgettigan, Pa" uniqKey="Mcgettigan P">PA McGettigan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kumar, S" uniqKey="Kumar S">S Kumar</name></author><author><name sortKey="Nei, M" uniqKey="Nei M">M Nei</name></author><author><name sortKey="Dudley, J" uniqKey="Dudley J">J Dudley</name></author><author><name sortKey="Tamura, K" uniqKey="Tamura K">K Tamura</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zwickl, Dj" uniqKey="Zwickl D">DJ Zwickl</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sukumaran, J" uniqKey="Sukumaran J">J Sukumaran</name></author><author><name sortKey="Holder, Mt" uniqKey="Holder M">MT Holder</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Potdar, Va" uniqKey="Potdar V">VA Potdar</name></author><author><name sortKey="Chadha, Ms" uniqKey="Chadha M">MS Chadha</name></author><author><name sortKey="Jadhav, Sm" uniqKey="Jadhav S">SM Jadhav</name></author><author><name sortKey="Mullick, J" uniqKey="Mullick J">J Mullick</name></author><author><name sortKey="Cherian, Ss" uniqKey="Cherian S">SS Cherian</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Page, Rd" uniqKey="Page R">RD Page</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Waterhouse, Am" uniqKey="Waterhouse A">AM Waterhouse</name></author><author><name sortKey="Procter, Jb" uniqKey="Procter J">JB Procter</name></author><author><name sortKey="Martin, Dm" uniqKey="Martin D">DM Martin</name></author><author><name sortKey="Clamp, M" uniqKey="Clamp M">M Clamp</name></author><author><name sortKey="Barton, Gj" uniqKey="Barton G">GJ Barton</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yusim, K" uniqKey="Yusim K">K Yusim</name></author><author><name sortKey="Kesmir, C" uniqKey="Kesmir C">C Kesmir</name></author><author><name sortKey="Gaschen, B" uniqKey="Gaschen B">B Gaschen</name></author><author><name sortKey="Addo, Mm" uniqKey="Addo M">MM Addo</name></author><author><name sortKey="Altfeld, M" uniqKey="Altfeld M">M Altfeld</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Poon, Af" uniqKey="Poon A">AF Poon</name></author><author><name sortKey="Lewis, Fi" uniqKey="Lewis F">FI Lewis</name></author><author><name sortKey="Pond, Sl" uniqKey="Pond S">SL Pond</name></author><author><name sortKey="Frost, Sd" uniqKey="Frost S">SD Frost</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kosakovsky Pond, Sl" uniqKey="Kosakovsky Pond S">SL Kosakovsky Pond</name></author><author><name sortKey="Frost, Sd" uniqKey="Frost S">SD Frost</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS One</journal-id><journal-id journal-id-type="iso-abbrev">PLoS ONE</journal-id><journal-id journal-id-type="publisher-id">plos</journal-id><journal-id journal-id-type="pmc">plosone</journal-id><journal-title-group><journal-title>PLoS ONE</journal-title></journal-title-group><issn pub-type="epub">1932-6203</issn><publisher><publisher-name>Public Library of Science</publisher-name><publisher-loc>San Francisco, USA</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">21249207</article-id><article-id pub-id-type="pmc">3017559</article-id><article-id pub-id-type="publisher-id">PONE-D-10-03213</article-id><article-id pub-id-type="doi">10.1371/journal.pone.0016087</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Biology</subject><subj-group><subject>Ecology</subject><subj-group><subject>Microbial Ecology</subject></subj-group></subj-group><subj-group><subject>Evolutionary Biology</subject><subj-group><subject>Evolutionary Processes</subject><subj-group><subject>Genetic Drift</subject></subj-group></subj-group><subj-group><subject>Genomic Evolution</subject></subj-group></subj-group><subj-group><subject>Genetics</subject><subj-group><subject>Population Genetics</subject><subj-group><subject>Genetic Polymorphism</subject></subj-group></subj-group></subj-group><subj-group><subject>Genomics</subject><subj-group><subject>Genome Evolution</subject><subject>Genome Sequencing</subject></subj-group></subj-group><subj-group><subject>Microbiology</subject><subj-group><subject>Virology</subject><subj-group><subject>Emerging Viral Diseases</subject><subject>Viral Evolution</subject><subject>Viral Immune Evasion</subject></subj-group></subj-group><subj-group><subject>Emerging Infectious Diseases</subject><subject>Host-Pathogen Interaction</subject><subject>Medical Microbiology</subject><subject>Microbial Evolution</subject><subject>Pathogenesis</subject></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Medicine</subject><subj-group><subject>Infectious Diseases</subject><subj-group><subject>Viral Diseases</subject><subj-group><subject>Influenza</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Veterinary Science</subject><subj-group><subject>Veterinary Diseases</subject><subj-group><subject>Veterinary Virology</subject></subj-group></subj-group></subj-group></article-categories><title-group><article-title>Nationwide Molecular Surveillance of Pandemic H1N1 Influenza A Virus Genomes: Canada, 2009</article-title><alt-title alt-title-type="running-head">A/H1N1pdm Genomes in Canada</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Graham</surname><given-names>Morag</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="aff" rid="aff2"><sup>2</sup></xref><xref ref-type="corresp" rid="cor1"><sup>*</sup></xref></contrib><contrib contrib-type="author"><name><surname>Liang</surname><given-names>Binhua</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Van Domselaar</surname><given-names>Gary</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="aff" rid="aff2"><sup>2</sup></xref><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Bastien</surname><given-names>Nathalie</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Beaudoin</surname><given-names>Carole</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="aff" rid="aff4"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Tyler</surname><given-names>Shaun</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kaplen</surname><given-names>Brynn</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Landry</surname><given-names>Erika</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><collab>the National Influenza A/H1N1pdm Genomics Study Team (NIGST)</collab><xref ref-type="author-notes" rid="fn1"><sup>¶</sup></xref></contrib><contrib contrib-type="author"><name><surname>Li</surname><given-names>Yan</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib></contrib-group><aff id="aff1"><label>1</label><addr-line>National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada</addr-line></aff><aff id="aff2"><label>2</label><addr-line>Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada</addr-line></aff><aff id="aff3"><label>3</label><addr-line>Department of Computer Science, University of Manitoba, Winnipeg, Manitoba, Canada</addr-line></aff><aff id="aff4"><label>4</label><addr-line>Department of Community Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada</addr-line></aff><contrib-group><contrib contrib-type="editor"><name><surname>Tse</surname><given-names>Herman</given-names></name><role>Editor</role><xref ref-type="aff" rid="edit1"></xref></contrib></contrib-group><aff id="edit1">The University of Hong Kong, Hong Kong</aff><author-notes><corresp id="cor1">* E-mail: <email>morag.graham@phac-aspc.gc.ca</email></corresp><fn fn-type="con"><p>Conceived and designed the experiments: MG GVD NB ST YL. Performed the experiments: NB ST BK EL. Analyzed the data: MG BL GVD NB CB. Contributed reagents/materials/analysis tools: BL NB YL CB NIGST. Wrote the paper: MG BL GVD CB NB.</p></fn><fn id="fn1" fn-type="other"><p>¶ For a full list of members of the National Influenza A/H1N1pdm Genomics Study Team (NIGST) please see the Acknowledgments section.</p></fn></author-notes><pub-date pub-type="collection"><year>2011</year></pub-date><pub-date pub-type="epub"><day>7</day><month>1</month><year>2011</year></pub-date><volume>6</volume><issue>1</issue><elocation-id>e16087</elocation-id><history><date date-type="received"><day>3</day><month>10</month><year>2010</year></date><date date-type="accepted"><day>6</day><month>12</month><year>2010</year></date></history><permissions><copyright-statement>Graham et al.</copyright-statement><copyright-year>2011</copyright-year><license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.</license-p></license></permissions><abstract><sec><title>Background</title><p>In April 2009, a novel triple-reassortant swine influenza A H1N1 virus (“A/H1N1pdm”; also known as SOIV) was detected and spread globally as the first influenza pandemic of the 21<sup>st</sup> century. Sequencing has since been conducted at an unprecedented rate globally in order to monitor the diversification of this emergent virus and to track mutations that may affect virus behavior.</p></sec><sec><title>Methodology/Principal Findings</title><p>By Sanger sequencing, we determined consensus whole-genome sequences for A/H1N1pdm viruses sampled nationwide in Canada over 33 weeks during the 2009 first and second pandemic waves. A total of 235 virus genomes sampled from unique subjects were analyzed, providing insight into the temporal and spatial trajectory of A/H1N1pdm lineages within Canada. Three clades (2, 3, and 7) were identifiable within the first two weeks of A/H1N1pdm appearance, with clades 5 and 6 appearing thereafter; further diversification was not apparent. Only two viral sites displayed evidence of adaptive evolution, located in hemagglutinin (HA) corresponding to D222 in the HA receptor-binding site, and to E374 at HA2-subunit position 47. Among the Canadian sampled viruses, we observed notable genetic diversity (1.47×10<sup>−3</sup> amino acid substitutions per site) in the gene encoding PB1, particularly within the viral genomic RNA (vRNA)-binding domain (residues 493–757). This genome data set supports the conclusion that A/H1N1pdm is evolving but not excessively relative to other H1N1 influenza A viruses. Entropy analysis was used to investigate whether any mutated A/H1N1pdm protein residues were associated with infection severity; however no virus genotypes were observed to trend with infection severity. One virus that harboured heterozygote coding mutations, including PB2 D567D/G, was attributed to a severe and potentially mixed infection; yet the functional significance of this PB2 mutation remains unknown.</p></sec><sec><title>Conclusions/Significance</title><p>These findings contribute to enhanced understanding of Influenza A/H1N1pdm viral dynamics.</p></sec></abstract><counts><page-count count="13"></page-count></counts></article-meta></front></pmc><affiliations><list><country><li>Canada</li></country><region><li>Manitoba</li></region><settlement><li>Winnipeg</li></settlement><orgName><li>Université du Manitoba</li></orgName></list><tree><country name="Canada"><noRegion><name sortKey="Graham, Morag" sort="Graham, Morag" uniqKey="Graham M" first="Morag" last="Graham">Morag Graham</name></noRegion><name sortKey="Bastien, Nathalie" sort="Bastien, Nathalie" uniqKey="Bastien N" first="Nathalie" last="Bastien">Nathalie Bastien</name><name sortKey="Beaudoin, Carole" sort="Beaudoin, Carole" uniqKey="Beaudoin C" first="Carole" last="Beaudoin">Carole Beaudoin</name><name sortKey="Beaudoin, Carole" sort="Beaudoin, Carole" uniqKey="Beaudoin C" first="Carole" last="Beaudoin">Carole Beaudoin</name><name sortKey="Graham, Morag" sort="Graham, Morag" uniqKey="Graham M" first="Morag" last="Graham">Morag Graham</name><name sortKey="Kaplen, Brynn" sort="Kaplen, Brynn" uniqKey="Kaplen B" first="Brynn" last="Kaplen">Brynn Kaplen</name><name sortKey="Landry, Erika" sort="Landry, Erika" uniqKey="Landry E" first="Erika" last="Landry">Erika Landry</name><name sortKey="Li, Yan" sort="Li, Yan" uniqKey="Li Y" first="Yan" last="Li">Yan Li</name><name sortKey="Li, Yan" sort="Li, Yan" uniqKey="Li Y" first="Yan" last="Li">Yan Li</name><name sortKey="Liang, Binhua" sort="Liang, Binhua" uniqKey="Liang B" first="Binhua" last="Liang">Binhua Liang</name><name sortKey="Tyler, Shaun" sort="Tyler, Shaun" uniqKey="Tyler S" first="Shaun" last="Tyler">Shaun Tyler</name><name sortKey="Van Domselaar, Gary" sort="Van Domselaar, Gary" uniqKey="Van Domselaar G" first="Gary" last="Van Domselaar">Gary Van Domselaar</name><name sortKey="Van Domselaar, Gary" sort="Van Domselaar, Gary" uniqKey="Van Domselaar G" first="Gary" last="Van Domselaar">Gary Van Domselaar</name><name sortKey="Van Domselaar, Gary" sort="Van Domselaar, Gary" uniqKey="Van Domselaar G" first="Gary" last="Van Domselaar">Gary Van Domselaar</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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