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In Silico Identification of Highly Conserved Epitopes of Influenza A H1N1, H2N2, H3N2, and H5N1 with Diagnostic and Vaccination Potential

Identifieur interne : 000435 ( Pmc/Checkpoint ); précédent : 000434; suivant : 000436

In Silico Identification of Highly Conserved Epitopes of Influenza A H1N1, H2N2, H3N2, and H5N1 with Diagnostic and Vaccination Potential

Auteurs : José Esteban Mu Oz-Medina [Mexique] ; Carlos Javier Sánchez-Vallejo [Mexique] ; Alfonso Méndez-Tenorio [Mexique] ; Irma Eloísa Monroy-Mu Oz [Mexique] ; Javier Angeles-Martínez [Mexique] ; Andrea Santos Coy-Arechavaleta [Mexique] ; Clara Esperanza Santacruz-Tinoco [Mexique] ; Joaquín González-Ibarra [Mexique] ; Yu-Mei Anguiano-Hernández [Mexique] ; César Raúl González-Bonilla [Mexique] ; Eva Ram N-Gallegos [Mexique] ; José Alberto Díaz-Qui Onez [Mexique]

Source :

RBID : PMC:4544958

Abstract

The unpredictable, evolutionary nature of the influenza A virus (IAV) is the primary problem when generating a vaccine and when designing diagnostic strategies; thus, it is necessary to determine the constant regions in viral proteins. In this study, we completed an in silico analysis of the reported epitopes of the 4 IAV proteins that are antigenically most significant (HA, NA, NP, and M2) in the 3 strains with the greatest world circulation in the last century (H1N1, H2N2, and H3N2) and in one of the main aviary subtypes responsible for zoonosis (H5N1). For this purpose, the HMMER program was used to align 3,016 epitopes reported in the Immune Epitope Database and Analysis Resource (IEDB) and distributed in 34,294 stored sequences in the Pfam database. Eighteen epitopes were identified: 8 in HA, 5 in NA, 3 in NP, and 2 in M2. These epitopes have remained constant since they were first identified (~91 years) and are present in strains that have circulated on 5 continents. These sites could be targets for vaccination design strategies based on epitopes and/or as markers in the implementation of diagnostic techniques.


Url:
DOI: 10.1155/2015/813047
PubMed: 26346523
PubMed Central: 4544958


Affiliations:


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PMC:4544958

Le document en format XML

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Identification of Highly Conserved Epitopes of Influenza A H1N1, H2N2, H3N2, and H5N1 with Diagnostic and Vaccination Potential</title>
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<name sortKey="Santacruz Tinoco, Clara Esperanza" sort="Santacruz Tinoco, Clara Esperanza" uniqKey="Santacruz Tinoco C" first="Clara Esperanza" last="Santacruz-Tinoco">Clara Esperanza Santacruz-Tinoco</name>
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<name sortKey="Gonzalez Ibarra, Joaquin" sort="Gonzalez Ibarra, Joaquin" uniqKey="Gonzalez Ibarra J" first="Joaquín" last="González-Ibarra">Joaquín González-Ibarra</name>
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<name sortKey="Anguiano Hernandez, Yu Mei" sort="Anguiano Hernandez, Yu Mei" uniqKey="Anguiano Hernandez Y" first="Yu-Mei" last="Anguiano-Hernández">Yu-Mei Anguiano-Hernández</name>
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<name sortKey="Gonzalez Bonilla, Cesar Raul" sort="Gonzalez Bonilla, Cesar Raul" uniqKey="Gonzalez Bonilla C" first="César Raúl" last="González-Bonilla">César Raúl González-Bonilla</name>
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<name sortKey="Ram N Gallegos, Eva" sort="Ram N Gallegos, Eva" uniqKey="Ram N Gallegos E" first="Eva" last="Ram N-Gallegos">Eva Ram N-Gallegos</name>
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<name sortKey="Diaz Qui Onez, Jose Alberto" sort="Diaz Qui Onez, Jose Alberto" uniqKey="Diaz Qui Onez J" first="José Alberto" last="Díaz-Qui Onez">José Alberto Díaz-Qui Onez</name>
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<title xml:lang="en" level="a" type="main">
<italic>In Silico</italic>
Identification of Highly Conserved Epitopes of Influenza A H1N1, H2N2, H3N2, and H5N1 with Diagnostic and Vaccination Potential</title>
<author>
<name sortKey="Mu Oz Medina, Jose Esteban" sort="Mu Oz Medina, Jose Esteban" uniqKey="Mu Oz Medina J" first="José Esteban" last="Mu Oz-Medina">José Esteban Mu Oz-Medina</name>
<affiliation wicri:level="1">
<nlm:aff id="I1">Laboratorio Central de Epidemiología, Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social, Avenida Jacarandas S/N, Esquina Circuito Interior, Colonia La Raza Delegación Azcapotzalco, 02990 México, DF, Mexico</nlm:aff>
<country xml:lang="fr">Mexique</country>
<wicri:regionArea>Laboratorio Central de Epidemiología, Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social, Avenida Jacarandas S/N, Esquina Circuito Interior, Colonia La Raza Delegación Azcapotzalco, 02990 México, DF</wicri:regionArea>
<wicri:noRegion>DF</wicri:noRegion>
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<author>
<name sortKey="Sanchez Vallejo, Carlos Javier" sort="Sanchez Vallejo, Carlos Javier" uniqKey="Sanchez Vallejo C" first="Carlos Javier" last="Sánchez-Vallejo">Carlos Javier Sánchez-Vallejo</name>
<affiliation wicri:level="1">
<nlm:aff id="I2">Laboratorio de Biotecnología y Bioinformática Genómica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Carpio y Plan de Ayala S/N, Colonia Plutarco Elías Calles, Delegación Miguel Hidalgo, 11340 México, DF, Mexico</nlm:aff>
<country xml:lang="fr">Mexique</country>
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<name sortKey="Mendez Tenorio, Alfonso" sort="Mendez Tenorio, Alfonso" uniqKey="Mendez Tenorio A" first="Alfonso" last="Méndez-Tenorio">Alfonso Méndez-Tenorio</name>
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<nlm:aff id="I2">Laboratorio de Biotecnología y Bioinformática Genómica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Carpio y Plan de Ayala S/N, Colonia Plutarco Elías Calles, Delegación Miguel Hidalgo, 11340 México, DF, Mexico</nlm:aff>
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<name sortKey="Monroy Mu Oz, Irma Eloisa" sort="Monroy Mu Oz, Irma Eloisa" uniqKey="Monroy Mu Oz I" first="Irma Eloísa" last="Monroy-Mu Oz">Irma Eloísa Monroy-Mu Oz</name>
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<nlm:aff id="I3">Laboratorio de Genómica, Departamento de Genética y Genómica Humana, Instituto Nacional de Perinatología “Isidro Espinosa de los Reyes”, Montes Urales 800, Colonia Lomas Virreyes, Delegación Miguel Hidalgo, 11000 México, DF, Mexico</nlm:aff>
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<author>
<name sortKey="Angeles Martinez, Javier" sort="Angeles Martinez, Javier" uniqKey="Angeles Martinez J" first="Javier" last="Angeles-Martínez">Javier Angeles-Martínez</name>
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<nlm:aff id="I4">Laboratorio de Genómica, Departamento de Biología Molecular, Instituto Nacional de Cardiología “Ignacio Chávez”, Juan Badiano No. 1, Colonia Sección XVI, Delegación Tlalpan, 14080 México, DF, Mexico</nlm:aff>
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<name sortKey="Santos Coy Arechavaleta, Andrea" sort="Santos Coy Arechavaleta, Andrea" uniqKey="Santos Coy Arechavaleta A" first="Andrea" last="Santos Coy-Arechavaleta">Andrea Santos Coy-Arechavaleta</name>
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<nlm:aff id="I1">Laboratorio Central de Epidemiología, Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social, Avenida Jacarandas S/N, Esquina Circuito Interior, Colonia La Raza Delegación Azcapotzalco, 02990 México, DF, Mexico</nlm:aff>
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<name sortKey="Santacruz Tinoco, Clara Esperanza" sort="Santacruz Tinoco, Clara Esperanza" uniqKey="Santacruz Tinoco C" first="Clara Esperanza" last="Santacruz-Tinoco">Clara Esperanza Santacruz-Tinoco</name>
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<nlm:aff id="I1">Laboratorio Central de Epidemiología, Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social, Avenida Jacarandas S/N, Esquina Circuito Interior, Colonia La Raza Delegación Azcapotzalco, 02990 México, DF, Mexico</nlm:aff>
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<name sortKey="Gonzalez Ibarra, Joaquin" sort="Gonzalez Ibarra, Joaquin" uniqKey="Gonzalez Ibarra J" first="Joaquín" last="González-Ibarra">Joaquín González-Ibarra</name>
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<nlm:aff id="I5">División de Laboratorios de Vigilancia e Investigación Epidemiológica, Instituto Mexicano del Seguro Social, Mier y Pesado No. 120, Colonia Del Valle, Delegación Benito Juárez, 03100 México, DF, Mexico</nlm:aff>
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<wicri:regionArea>División de Laboratorios de Vigilancia e Investigación Epidemiológica, Instituto Mexicano del Seguro Social, Mier y Pesado No. 120, Colonia Del Valle, Delegación Benito Juárez, 03100 México, DF</wicri:regionArea>
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<author>
<name sortKey="Anguiano Hernandez, Yu Mei" sort="Anguiano Hernandez, Yu Mei" uniqKey="Anguiano Hernandez Y" first="Yu-Mei" last="Anguiano-Hernández">Yu-Mei Anguiano-Hernández</name>
<affiliation wicri:level="1">
<nlm:aff id="I1">Laboratorio Central de Epidemiología, Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social, Avenida Jacarandas S/N, Esquina Circuito Interior, Colonia La Raza Delegación Azcapotzalco, 02990 México, DF, Mexico</nlm:aff>
<country xml:lang="fr">Mexique</country>
<wicri:regionArea>Laboratorio Central de Epidemiología, Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social, Avenida Jacarandas S/N, Esquina Circuito Interior, Colonia La Raza Delegación Azcapotzalco, 02990 México, DF</wicri:regionArea>
<wicri:noRegion>DF</wicri:noRegion>
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<author>
<name sortKey="Gonzalez Bonilla, Cesar Raul" sort="Gonzalez Bonilla, Cesar Raul" uniqKey="Gonzalez Bonilla C" first="César Raúl" last="González-Bonilla">César Raúl González-Bonilla</name>
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<nlm:aff id="I5">División de Laboratorios de Vigilancia e Investigación Epidemiológica, Instituto Mexicano del Seguro Social, Mier y Pesado No. 120, Colonia Del Valle, Delegación Benito Juárez, 03100 México, DF, Mexico</nlm:aff>
<country xml:lang="fr">Mexique</country>
<wicri:regionArea>División de Laboratorios de Vigilancia e Investigación Epidemiológica, Instituto Mexicano del Seguro Social, Mier y Pesado No. 120, Colonia Del Valle, Delegación Benito Juárez, 03100 México, DF</wicri:regionArea>
<wicri:noRegion>DF</wicri:noRegion>
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<author>
<name sortKey="Ram N Gallegos, Eva" sort="Ram N Gallegos, Eva" uniqKey="Ram N Gallegos E" first="Eva" last="Ram N-Gallegos">Eva Ram N-Gallegos</name>
<affiliation wicri:level="1">
<nlm:aff id="I6">Laboratorio de Citopatologia Ambiental, Departamento de Morfología, Escuela Nacional de Ciencias Biológicas Campus Zacatenco, Instituto Politécnico Nacional, Wilfrido Massieu S/N, Colonia Nueva Industrial Vallejo, Delegación Gustavo A. Madero, 07738 México, DF, Mexico</nlm:aff>
<country xml:lang="fr">Mexique</country>
<wicri:regionArea>Laboratorio de Citopatologia Ambiental, Departamento de Morfología, Escuela Nacional de Ciencias Biológicas Campus Zacatenco, Instituto Politécnico Nacional, Wilfrido Massieu S/N, Colonia Nueva Industrial Vallejo, Delegación Gustavo A. Madero, 07738 México, DF</wicri:regionArea>
<wicri:noRegion>DF</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Diaz Qui Onez, Jose Alberto" sort="Diaz Qui Onez, Jose Alberto" uniqKey="Diaz Qui Onez J" first="José Alberto" last="Díaz-Qui Onez">José Alberto Díaz-Qui Onez</name>
<affiliation wicri:level="1">
<nlm:aff id="I7">Instituto de Diagnóstico y Referencia Epidemiológicos “Manuel Martínez Báez”, Francisco de P. Miranda No. 177, Colonia Unidad Lomas de Plateros, Delegación Álvaro Obregón, 01480 México, DF, Mexico</nlm:aff>
<country xml:lang="fr">Mexique</country>
<wicri:regionArea>Instituto de Diagnóstico y Referencia Epidemiológicos “Manuel Martínez Báez”, Francisco de P. Miranda No. 177, Colonia Unidad Lomas de Plateros, Delegación Álvaro Obregón, 01480 México, DF</wicri:regionArea>
<wicri:noRegion>DF</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="I8">Facultad de Medicina, Universidad Nacional Autónoma de México, Avenida Universidad 3000, Colonia Copilco Universidad, Delegación Coyoacán, 04510 México, DF, Mexico</nlm:aff>
<country xml:lang="fr">Mexique</country>
<wicri:regionArea>Facultad de Medicina, Universidad Nacional Autónoma de México, Avenida Universidad 3000, Colonia Copilco Universidad, Delegación Coyoacán, 04510 México, DF</wicri:regionArea>
<wicri:noRegion>DF</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series>
<title level="j">BioMed Research International</title>
<idno type="ISSN">2314-6133</idno>
<idno type="eISSN">2314-6141</idno>
<imprint>
<date when="2015">2015</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass></textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<p>The unpredictable, evolutionary nature of the influenza A virus (IAV) is the primary problem when generating a vaccine and when designing diagnostic strategies; thus, it is necessary to determine the constant regions in viral proteins. In this study, we completed an
<italic>in silico</italic>
analysis of the reported epitopes of the 4 IAV proteins that are antigenically most significant (HA, NA, NP, and M2) in the 3 strains with the greatest world circulation in the last century (H1N1, H2N2, and H3N2) and in one of the main aviary subtypes responsible for zoonosis (H5N1). For this purpose, the HMMER program was used to align 3,016 epitopes reported in the Immune Epitope Database and Analysis Resource (IEDB) and distributed in 34,294 stored sequences in the Pfam database. Eighteen epitopes were identified: 8 in HA, 5 in NA, 3 in NP, and 2 in M2. These epitopes have remained constant since they were first identified (~91 years) and are present in strains that have circulated on 5 continents. These sites could be targets for vaccination design strategies based on epitopes and/or as markers in the implementation of diagnostic techniques.</p>
</div>
</front>
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</TEI>
<pmc article-type="research-article">
<pmc-dir>properties open_access</pmc-dir>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">Biomed Res Int</journal-id>
<journal-id journal-id-type="iso-abbrev">Biomed Res Int</journal-id>
<journal-id journal-id-type="publisher-id">BMRI</journal-id>
<journal-title-group>
<journal-title>BioMed Research International</journal-title>
</journal-title-group>
<issn pub-type="ppub">2314-6133</issn>
<issn pub-type="epub">2314-6141</issn>
<publisher>
<publisher-name>Hindawi Publishing Corporation</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">26346523</article-id>
<article-id pub-id-type="pmc">4544958</article-id>
<article-id pub-id-type="doi">10.1155/2015/813047</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Research Article</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>
<italic>In Silico</italic>
Identification of Highly Conserved Epitopes of Influenza A H1N1, H2N2, H3N2, and H5N1 with Diagnostic and Vaccination Potential</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Muñoz-Medina</surname>
<given-names>José Esteban</given-names>
</name>
<xref ref-type="aff" rid="I1">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Sánchez-Vallejo</surname>
<given-names>Carlos Javier</given-names>
</name>
<xref ref-type="aff" rid="I2">
<sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Méndez-Tenorio</surname>
<given-names>Alfonso</given-names>
</name>
<xref ref-type="aff" rid="I2">
<sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Monroy-Muñoz</surname>
<given-names>Irma Eloísa</given-names>
</name>
<xref ref-type="aff" rid="I3">
<sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Angeles-Martínez</surname>
<given-names>Javier</given-names>
</name>
<xref ref-type="aff" rid="I4">
<sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Santos Coy-Arechavaleta</surname>
<given-names>Andrea</given-names>
</name>
<xref ref-type="aff" rid="I1">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Santacruz-Tinoco</surname>
<given-names>Clara Esperanza</given-names>
</name>
<xref ref-type="aff" rid="I1">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>González-Ibarra</surname>
<given-names>Joaquín</given-names>
</name>
<xref ref-type="aff" rid="I5">
<sup>5</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Anguiano-Hernández</surname>
<given-names>Yu-Mei</given-names>
</name>
<xref ref-type="aff" rid="I1">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>González-Bonilla</surname>
<given-names>César Raúl</given-names>
</name>
<xref ref-type="aff" rid="I5">
<sup>5</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Ramón-Gallegos</surname>
<given-names>Eva</given-names>
</name>
<xref ref-type="aff" rid="I6">
<sup>6</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Díaz-Quiñonez</surname>
<given-names>José Alberto</given-names>
</name>
<xref ref-type="aff" rid="I7">
<sup>7</sup>
</xref>
<xref ref-type="aff" rid="I8">
<sup>8</sup>
</xref>
<xref ref-type="corresp" rid="cor1">
<sup>*</sup>
</xref>
</contrib>
</contrib-group>
<aff id="I1">
<sup>1</sup>
Laboratorio Central de Epidemiología, Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social, Avenida Jacarandas S/N, Esquina Circuito Interior, Colonia La Raza Delegación Azcapotzalco, 02990 México, DF, Mexico</aff>
<aff id="I2">
<sup>2</sup>
Laboratorio de Biotecnología y Bioinformática Genómica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Carpio y Plan de Ayala S/N, Colonia Plutarco Elías Calles, Delegación Miguel Hidalgo, 11340 México, DF, Mexico</aff>
<aff id="I3">
<sup>3</sup>
Laboratorio de Genómica, Departamento de Genética y Genómica Humana, Instituto Nacional de Perinatología “Isidro Espinosa de los Reyes”, Montes Urales 800, Colonia Lomas Virreyes, Delegación Miguel Hidalgo, 11000 México, DF, Mexico</aff>
<aff id="I4">
<sup>4</sup>
Laboratorio de Genómica, Departamento de Biología Molecular, Instituto Nacional de Cardiología “Ignacio Chávez”, Juan Badiano No. 1, Colonia Sección XVI, Delegación Tlalpan, 14080 México, DF, Mexico</aff>
<aff id="I5">
<sup>5</sup>
División de Laboratorios de Vigilancia e Investigación Epidemiológica, Instituto Mexicano del Seguro Social, Mier y Pesado No. 120, Colonia Del Valle, Delegación Benito Juárez, 03100 México, DF, Mexico</aff>
<aff id="I6">
<sup>6</sup>
Laboratorio de Citopatologia Ambiental, Departamento de Morfología, Escuela Nacional de Ciencias Biológicas Campus Zacatenco, Instituto Politécnico Nacional, Wilfrido Massieu S/N, Colonia Nueva Industrial Vallejo, Delegación Gustavo A. Madero, 07738 México, DF, Mexico</aff>
<aff id="I7">
<sup>7</sup>
Instituto de Diagnóstico y Referencia Epidemiológicos “Manuel Martínez Báez”, Francisco de P. Miranda No. 177, Colonia Unidad Lomas de Plateros, Delegación Álvaro Obregón, 01480 México, DF, Mexico</aff>
<aff id="I8">
<sup>8</sup>
Facultad de Medicina, Universidad Nacional Autónoma de México, Avenida Universidad 3000, Colonia Copilco Universidad, Delegación Coyoacán, 04510 México, DF, Mexico</aff>
<author-notes>
<corresp id="cor1">*José Alberto Díaz-Quiñonez:
<email>alberto.diaz@salud.gob.mx</email>
</corresp>
<fn fn-type="other">
<p>Academic Editor: Swapnil Sinha</p>
</fn>
</author-notes>
<pub-date pub-type="ppub">
<year>2015</year>
</pub-date>
<pub-date pub-type="epub">
<day>6</day>
<month>8</month>
<year>2015</year>
</pub-date>
<volume>2015</volume>
<elocation-id>813047</elocation-id>
<history>
<date date-type="received">
<day>22</day>
<month>2</month>
<year>2015</year>
</date>
<date date-type="rev-recd">
<day>13</day>
<month>6</month>
<year>2015</year>
</date>
<date date-type="accepted">
<day>14</day>
<month>6</month>
<year>2015</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright © 2015 José Esteban Muñoz-Medina et al.</copyright-statement>
<copyright-year>2015</copyright-year>
<license xlink:href="https://creativecommons.org/licenses/by/3.0/">
<license-p>This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
</license>
</permissions>
<abstract>
<p>The unpredictable, evolutionary nature of the influenza A virus (IAV) is the primary problem when generating a vaccine and when designing diagnostic strategies; thus, it is necessary to determine the constant regions in viral proteins. In this study, we completed an
<italic>in silico</italic>
analysis of the reported epitopes of the 4 IAV proteins that are antigenically most significant (HA, NA, NP, and M2) in the 3 strains with the greatest world circulation in the last century (H1N1, H2N2, and H3N2) and in one of the main aviary subtypes responsible for zoonosis (H5N1). For this purpose, the HMMER program was used to align 3,016 epitopes reported in the Immune Epitope Database and Analysis Resource (IEDB) and distributed in 34,294 stored sequences in the Pfam database. Eighteen epitopes were identified: 8 in HA, 5 in NA, 3 in NP, and 2 in M2. These epitopes have remained constant since they were first identified (~91 years) and are present in strains that have circulated on 5 continents. These sites could be targets for vaccination design strategies based on epitopes and/or as markers in the implementation of diagnostic techniques.</p>
</abstract>
</article-meta>
</front>
<floats-group>
<fig id="fig1" orientation="portrait" position="float">
<label>Figure 1</label>
<caption>
<p>Flowchart of the stages and programs utilized in this study.</p>
</caption>
<graphic xlink:href="BMRI2015-813047.001"></graphic>
</fig>
<fig id="fig2" orientation="portrait" position="float">
<label>Figure 2</label>
<caption>
<p>Example of the frequency distribution graph generated using the
<italic> hmmalign</italic>
program for hemagglutinin of the H2N2 subtype. The arrows indicate the selected regions for this protein.</p>
</caption>
<graphic xlink:href="BMRI2015-813047.002"></graphic>
</fig>
<fig id="fig3" orientation="portrait" position="float">
<label>Figure 3</label>
<caption>
<p>Example of the epitope alignment completed using the Megalign program. The depicted figure corresponds to the hemagglutinin of the H3N2 subtype. The blue lines show the consensus sequences in the different epitopes reported.</p>
</caption>
<graphic xlink:href="BMRI2015-813047.003"></graphic>
</fig>
<fig id="fig4" orientation="portrait" position="float">
<label>Figure 4</label>
<caption>
<p>Three-dimensional localization of consensus epitopes. The protein structures are shown in green, and the conserved epitopes are shown as blue, yellow, and cyan spheres. The mutations within the consensus epitopes, compared to the current strains, are shown as red spheres. (a) [PDB: 2WR3] HA H1N1 in blue
<sup>127</sup>
SVSSFERFEIFPK
<sup>136</sup>
; in cyan
<sup>333</sup>
VTGLRNIPSIQSRGL
<sup>346</sup>
(b) [PDB: 2WRD] HA H2N2 in blue
<sup>204</sup>
LYQNVGTYVSVGTST
<sup>218</sup>
; in yellow
<sup>255</sup>
FESTGNLIAPEYGFKIS
<sup>271</sup>
; in cyan
<sup>337</sup>
IESRGLFGAIAGFIEGGWQ
<sup>355</sup>
(c) [PDB: 2YP2] HA H3N2 in blue
<sup>113</sup>
CYPYDVPDYASLRS
<sup>126</sup>
; in cyan
<sup>324</sup>
YVKQNTLKLA
<sup>333</sup>
(d) [PDB: 4BGW] HA H5N1 in yellow
<sup>229</sup>
IATRSKVNGQSGRM
<sup>243</sup>
(e) [PDB: 4B7J] NA H1N1 in blue
<sup>96</sup>
GWAIYSKDNNS
<sup>106</sup>
; in yellow
<sup>206</sup>
LKYNGIITETIKSW
<sup>219</sup>
(f) [PDB: 4GZQ] NA H3N2 in yellow
<sup>314</sup>
SSYVCSGLVGDTPR
<sup>327</sup>
(g) [PDB: 4B7J] NA H5N1 in blue
<sup>105</sup>
SHLECRTFFLTQGALLNDKH
<sup>124</sup>
; in cyan
<sup>234</sup>
KIFKMEKGKVVKSVEL
<sup>249</sup>
(h) NP H5N1 in blue
<sup>192</sup>
ELIRMIKRGINDRNFWR
<sup>208</sup>
; in yellow
<sup>261</sup>
RSALILRGSVAHKSCL
<sup>276</sup>
; in cyan
<sup>401</sup>
ASAGQISVQPTFSVQRN
<sup>417 </sup>
(i) [PDB: 2RLF] M2 H1N1 in blue
<sup>29</sup>
AASIIGILHLIL
<sup>40</sup>
; in yellow
<sup>51</sup>
ITRLFKHGLK
<sup>60</sup>
.</p>
</caption>
<graphic xlink:href="BMRI2015-813047.004"></graphic>
</fig>
<fig id="fig5" orientation="portrait" position="float">
<label>Figure 5</label>
<caption>
<p>The red circle indicates the sequence in which the epitope was first identified. The blue circle shows the 2013-2014 season vaccine strain, in the case of H1N1 and H3N2, and the current strain, in the case of H5N1. The evolutionary history was inferred using the Neighbor-Joining method. The following branch shows the replication percentages with which the taxa associated in the bootstrap test. The trees are drawn to scale, with the longest of the branches in the same units of evolutionary distance used to infer the phylogenetic tree. The evolutionary distance was calculated using the Poisson method and is presented in substitution site units. The analysis was completed using the MEGA 6 program. Shown are (a) the optimum tree with a sum of branches of 0.43300672; (b) the optimum tree with a sum of branches of 0.30107033; (c) the optimum tree with a sum of branches of 0.20974655; (d) the optimum tree with a sum of branches of 0.29223355; (e) the optimum tree with a sum of branches of 0.07724998; (f) the optimum tree with a sum of branches of 0.28312403.</p>
</caption>
<graphic xlink:href="BMRI2015-813047.005"></graphic>
</fig>
<fig id="fig6" orientation="portrait" position="float">
<label>Figure 6</label>
<caption>
<p>Geographic distribution of consensus epitopes. The countries in which the isolates containing the consensus epitopes defined in this study have been obtained are shown on the map.</p>
</caption>
<graphic xlink:href="BMRI2015-813047.006"></graphic>
</fig>
<table-wrap id="tab1" orientation="portrait" position="float">
<label>Table 1</label>
<caption>
<p>Distribution of epitopes and sequences obtained for each subtype.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" rowspan="1" colspan="1"></th>
<th align="center" colspan="5" rowspan="1">Viral strains</th>
</tr>
<tr>
<th align="left" rowspan="1" colspan="1"></th>
<th align="center" rowspan="1" colspan="1"></th>
<th align="center" rowspan="1" colspan="1">H1N1</th>
<th align="center" rowspan="1" colspan="1">H2N2</th>
<th align="center" rowspan="1" colspan="1">H3N2</th>
<th align="center" rowspan="1" colspan="1">H5N1</th>
</tr>
<tr>
<th align="left" rowspan="1" colspan="1"></th>
<th align="center" rowspan="1" colspan="1"></th>
<th align="center" rowspan="1" colspan="1">
<italic>n</italic>
(%)</th>
<th align="center" rowspan="1" colspan="1">
<italic>n</italic>
(%)</th>
<th align="center" rowspan="1" colspan="1">
<italic>n</italic>
(%)</th>
<th align="center" rowspan="1" colspan="1">
<italic>n</italic>
(%)</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">HA</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td align="left" rowspan="11" colspan="1">Proteins</td>
<td align="center" rowspan="1" colspan="1"> E</td>
<td align="center" rowspan="1" colspan="1">686 (50.7)</td>
<td align="center" rowspan="1" colspan="1">43 (47.3)</td>
<td align="center" rowspan="1" colspan="1">525 (52.2)</td>
<td align="center" rowspan="1" colspan="1">384 (67.8)</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1"> S</td>
<td align="center" rowspan="1" colspan="1">8416 (55.7)</td>
<td align="center" rowspan="1" colspan="1">175 (42.5)</td>
<td align="center" rowspan="1" colspan="1">7313 (60.0)</td>
<td align="center" rowspan="1" colspan="1">3024 (45.9)</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">NA</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1"> E</td>
<td align="center" rowspan="1" colspan="1">283 (20.9)</td>
<td align="center" rowspan="1" colspan="1">0 (0)</td>
<td align="center" rowspan="1" colspan="1">195 (19.4)</td>
<td align="center" rowspan="1" colspan="1">126 (22.2)</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1"> S</td>
<td align="center" rowspan="1" colspan="1">4462 (29.6)</td>
<td align="center" rowspan="1" colspan="1">129 (31.3)</td>
<td align="center" rowspan="1" colspan="1">2909 (23.9)</td>
<td align="center" rowspan="1" colspan="1">1981 (30.0)</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">NP</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1"> E</td>
<td align="center" rowspan="1" colspan="1">328 (24.3)</td>
<td align="center" rowspan="1" colspan="1">47 (51.6)</td>
<td align="center" rowspan="1" colspan="1">252 (25.0)</td>
<td align="center" rowspan="1" colspan="1">45 (7.9)</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1"> S</td>
<td align="center" rowspan="1" colspan="1">1225 (8.1)</td>
<td align="center" rowspan="1" colspan="1">78 (18.9)</td>
<td align="center" rowspan="1" colspan="1">1096 (9.0)</td>
<td align="center" rowspan="1" colspan="1">1019 (15.5)</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">M2</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1"> E</td>
<td align="center" rowspan="1" colspan="1">55 (4.1)</td>
<td align="center" rowspan="1" colspan="1">1 (1.1)</td>
<td align="center" rowspan="1" colspan="1">34 (3.4)</td>
<td align="center" rowspan="1" colspan="1">12 (2.1)</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1"> S</td>
<td align="center" rowspan="1" colspan="1">999 (6.6)</td>
<td align="center" rowspan="1" colspan="1">30 (7.3)</td>
<td align="center" rowspan="1" colspan="1">868 (7.1)</td>
<td align="center" rowspan="1" colspan="1">570 (8.6)</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn>
<p>Note: S = sequences and E = epitopes.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="tab2" orientation="portrait" position="float">
<label>Table 2</label>
<caption>
<p>Sites with the greatest frequency of epitopes.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" rowspan="1" colspan="1">Subtype</th>
<th align="center" rowspan="1" colspan="1">Protein</th>
<th align="center" rowspan="1" colspan="1">Site</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" rowspan="4" colspan="1">H1N1</td>
<td align="center" rowspan="1" colspan="1">HA</td>
<td align="center" rowspan="1" colspan="1">123–140; 205–219; 330–352</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">NA</td>
<td align="center" rowspan="1" colspan="1">93–109; 204–222</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">NP</td>
<td align="center" rowspan="1" colspan="1">414–427</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">M2</td>
<td align="center" rowspan="1" colspan="1">25–43; 48–62</td>
</tr>
<tr>
<td align="center" colspan="3" rowspan="1">
<hr></hr>
</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">H2N2</td>
<td align="center" rowspan="1" colspan="1">HA</td>
<td align="center" rowspan="1" colspan="1">200–220; 251–274; 332–356</td>
</tr>
<tr>
<td align="center" colspan="3" rowspan="1">
<hr></hr>
</td>
</tr>
<tr>
<td align="left" rowspan="3" colspan="1">H3N2</td>
<td align="center" rowspan="1" colspan="1">HA</td>
<td align="center" rowspan="1" colspan="1">112–131; 322–336;</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">NA</td>
<td align="center" rowspan="1" colspan="1">143–160; 311–331</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">NP</td>
<td align="center" rowspan="1" colspan="1">52–69; 363–378</td>
</tr>
<tr>
<td align="center" colspan="3" rowspan="1">
<hr></hr>
</td>
</tr>
<tr>
<td align="left" rowspan="3" colspan="1">H5N1</td>
<td align="center" rowspan="1" colspan="1">HA</td>
<td align="center" rowspan="1" colspan="1">174–195; 227–246; 247–267</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">NA</td>
<td align="center" rowspan="1" colspan="1">103–121; 231–252</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">NP</td>
<td align="center" rowspan="1" colspan="1">190–211; 257–278; 400–418</td>
</tr>
</tbody>
</table>
</table-wrap>
<table-wrap id="tab3" orientation="portrait" position="float">
<label>Table 3</label>
<caption>
<p>Consensus epitopes.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" rowspan="1" colspan="1">Subtype</th>
<th align="center" rowspan="1" colspan="1">Protein</th>
<th align="center" rowspan="1" colspan="1">Epitope</th>
<th align="left" rowspan="1" colspan="1">Sequence</th>
<th align="center" rowspan="1" colspan="1">T or B cell</th>
<th align="center" rowspan="1" colspan="1">Reference</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" rowspan="6" colspan="1">H1N1</td>
<td align="center" rowspan="2" colspan="1">HA</td>
<td align="center" rowspan="1" colspan="1">1</td>
<td align="left" rowspan="1" colspan="1">
<sup>127</sup>
SVSSFERFEIFPK
<sup>136</sup>
</td>
<td align="center" rowspan="1" colspan="1">T</td>
<td align="center" rowspan="1" colspan="1">[
<xref rid="B28" ref-type="bibr">28</xref>
]</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">2</td>
<td align="left" rowspan="1" colspan="1">
<sup>333</sup>
VTGLRNIPSIQSRGL
<sup>346</sup>
</td>
<td align="center" rowspan="1" colspan="1">T y B</td>
<td align="center" rowspan="1" colspan="1">[
<xref rid="B29" ref-type="bibr">29</xref>
,
<xref rid="B30" ref-type="bibr">30</xref>
]</td>
</tr>
<tr>
<td align="center" rowspan="2" colspan="1">NA</td>
<td align="center" rowspan="1" colspan="1">3</td>
<td align="left" rowspan="1" colspan="1">
<sup>96</sup>
GWAIYSKDNNS
<sup>106</sup>
</td>
<td align="center" rowspan="1" colspan="1">T</td>
<td align="center" rowspan="1" colspan="1">[
<xref rid="B31" ref-type="bibr">31</xref>
]</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">4</td>
<td align="left" rowspan="1" colspan="1">
<sup>206</sup>
LKYNGIITETIKSW
<sup>219</sup>
</td>
<td align="center" rowspan="1" colspan="1">T</td>
<td align="center" rowspan="1" colspan="1">[
<xref rid="B32" ref-type="bibr">32</xref>
]</td>
</tr>
<tr>
<td align="center" rowspan="2" colspan="1">M2</td>
<td align="center" rowspan="1" colspan="1">5</td>
<td align="left" rowspan="1" colspan="1">
<sup>29</sup>
AASIIGILHLIL
<sup>40</sup>
</td>
<td align="center" rowspan="1" colspan="1">T</td>
<td align="center" rowspan="1" colspan="1">[
<xref rid="B33" ref-type="bibr">33</xref>
]</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">6</td>
<td align="left" rowspan="1" colspan="1">
<sup>51</sup>
ITRLFKHGLK
<sup>60</sup>
</td>
<td align="center" rowspan="1" colspan="1">T</td>
<td align="center" rowspan="1" colspan="1">[
<xref rid="B32" ref-type="bibr">32</xref>
]</td>
</tr>
<tr>
<td align="center" colspan="6" rowspan="1">
<hr></hr>
</td>
</tr>
<tr>
<td align="left" rowspan="3" colspan="1">H2N2</td>
<td align="center" rowspan="3" colspan="1">HA</td>
<td align="center" rowspan="1" colspan="1">7</td>
<td align="left" rowspan="1" colspan="1">
<sup>204</sup>
LYQNVGTYVSVGTST
<sup>218</sup>
</td>
<td align="center" rowspan="1" colspan="1">T</td>
<td align="center" rowspan="1" colspan="1">[
<xref rid="B34" ref-type="bibr">34</xref>
]</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">8</td>
<td align="left" rowspan="1" colspan="1">
<sup>255</sup>
FESTGNLIAPEYGFKIS
<sup>271</sup>
</td>
<td align="center" rowspan="1" colspan="1">T</td>
<td align="center" rowspan="1" colspan="1">[
<xref rid="B28" ref-type="bibr">28</xref>
]</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">9</td>
<td align="left" rowspan="1" colspan="1">
<sup>337</sup>
IESRGLFGAIAGFIEGGWQ
<sup>355</sup>
</td>
<td align="center" rowspan="1" colspan="1">T</td>
<td align="center" rowspan="1" colspan="1">[
<xref rid="B35" ref-type="bibr">35</xref>
]</td>
</tr>
<tr>
<td align="center" colspan="6" rowspan="1">
<hr></hr>
</td>
</tr>
<tr>
<td align="left" rowspan="3" colspan="1">H3N2</td>
<td align="center" rowspan="2" colspan="1">HA</td>
<td align="center" rowspan="1" colspan="1">10</td>
<td align="left" rowspan="1" colspan="1">
<sup>113</sup>
CYPYDVPDYASLRS
<sup>126</sup>
</td>
<td align="center" rowspan="1" colspan="1">T y B</td>
<td align="center" rowspan="1" colspan="1">[
<xref rid="B32" ref-type="bibr">32</xref>
,
<xref rid="B36" ref-type="bibr">36</xref>
]</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">11</td>
<td align="left" rowspan="1" colspan="1">
<sup>324</sup>
YVKQNTLKLA
<sup>333</sup>
</td>
<td align="center" rowspan="1" colspan="1">T y B</td>
<td align="center" rowspan="1" colspan="1">[
<xref rid="B37" ref-type="bibr">37</xref>
,
<xref rid="B38" ref-type="bibr">38</xref>
]</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">NA</td>
<td align="center" rowspan="1" colspan="1">12</td>
<td align="left" rowspan="1" colspan="1">
<sup>314</sup>
SSYVCSGLVGDTPR
<sup>327</sup>
</td>
<td align="center" rowspan="1" colspan="1">T</td>
<td align="center" rowspan="1" colspan="1">[
<xref rid="B39" ref-type="bibr">39</xref>
]</td>
</tr>
<tr>
<td align="center" colspan="6" rowspan="1">
<hr></hr>
</td>
</tr>
<tr>
<td align="left" rowspan="6" colspan="1">H5N1</td>
<td align="center" rowspan="1" colspan="1">HA</td>
<td align="center" rowspan="1" colspan="1">13</td>
<td align="left" rowspan="1" colspan="1">
<sup>229</sup>
IATRSKVNGQSGRM
<sup>243</sup>
</td>
<td align="center" rowspan="1" colspan="1">T y B</td>
<td align="center" rowspan="1" colspan="1">[
<xref rid="B32" ref-type="bibr">32</xref>
,
<xref rid="B40" ref-type="bibr">40</xref>
]</td>
</tr>
<tr>
<td align="center" rowspan="2" colspan="1">NA</td>
<td align="center" rowspan="1" colspan="1">14</td>
<td align="left" rowspan="1" colspan="1">
<sup>105</sup>
SHLECRTFFLTQGALLNDKH
<sup>124</sup>
</td>
<td align="center" rowspan="1" colspan="1">T y B</td>
<td align="center" rowspan="1" colspan="1">[
<xref rid="B41" ref-type="bibr">41</xref>
,
<xref rid="B42" ref-type="bibr">42</xref>
]</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">15</td>
<td align="left" rowspan="1" colspan="1">
<sup>234</sup>
KIFKMEKGKVVKSVEL
<sup>249</sup>
</td>
<td align="center" rowspan="1" colspan="1">T y B</td>
<td align="center" rowspan="1" colspan="1">[
<xref rid="B32" ref-type="bibr">32</xref>
,
<xref rid="B41" ref-type="bibr">41</xref>
]</td>
</tr>
<tr>
<td align="center" rowspan="3" colspan="1">NP</td>
<td align="center" rowspan="1" colspan="1">16</td>
<td align="left" rowspan="1" colspan="1">
<sup>192</sup>
ELIRMIKRGINDRNFWR
<sup>208</sup>
</td>
<td align="center" rowspan="1" colspan="1">T</td>
<td align="center" rowspan="1" colspan="1">[
<xref rid="B43" ref-type="bibr">43</xref>
]</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">17</td>
<td align="left" rowspan="1" colspan="1">
<sup>261</sup>
RSALILRGSVAHKSCL
<sup>276</sup>
</td>
<td align="center" rowspan="1" colspan="1">T</td>
<td align="center" rowspan="1" colspan="1">[
<xref rid="B39" ref-type="bibr">39</xref>
]</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">18</td>
<td align="left" rowspan="1" colspan="1">
<sup>401</sup>
ASAGQISVQPTFSVQRN
<sup>417</sup>
</td>
<td align="center" rowspan="1" colspan="1">T</td>
<td align="center" rowspan="1" colspan="1">[
<xref rid="B39" ref-type="bibr">39</xref>
]</td>
</tr>
</tbody>
</table>
</table-wrap>
<table-wrap id="tab4" orientation="portrait" position="float">
<label>Table 4</label>
<caption>
<p>PDB accession codes.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" rowspan="1" colspan="1">Subtype</th>
<th align="center" rowspan="1" colspan="1">Protein</th>
<th align="center" rowspan="1" colspan="1">PDB codes</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" rowspan="3" colspan="1">H1N1</td>
<td align="center" rowspan="1" colspan="1">HA</td>
<td align="center" rowspan="1" colspan="1">2WR3</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">NA</td>
<td align="center" rowspan="1" colspan="1">4B7J</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">M2</td>
<td align="center" rowspan="1" colspan="1">2RLF</td>
</tr>
<tr>
<td align="center" colspan="3" rowspan="1">
<hr></hr>
</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">H2N2</td>
<td align="center" rowspan="1" colspan="1">HA</td>
<td align="center" rowspan="1" colspan="1">2WRD</td>
</tr>
<tr>
<td align="center" colspan="3" rowspan="1">
<hr></hr>
</td>
</tr>
<tr>
<td align="left" rowspan="2" colspan="1">H3N2</td>
<td align="center" rowspan="1" colspan="1">HA</td>
<td align="center" rowspan="1" colspan="1">2YP2</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">NA</td>
<td align="center" rowspan="1" colspan="1">4GZQ</td>
</tr>
<tr>
<td align="center" colspan="3" rowspan="1">
<hr></hr>
</td>
</tr>
<tr>
<td align="left" rowspan="3" colspan="1">H5N1</td>
<td align="center" rowspan="1" colspan="1">HA</td>
<td align="center" rowspan="1" colspan="1">4BGW</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">NA</td>
<td align="center" rowspan="1" colspan="1">4B7J</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">NP</td>
<td align="center" rowspan="1" colspan="1">3TC6</td>
</tr>
</tbody>
</table>
</table-wrap>
</floats-group>
</pmc>
<affiliations>
<list>
<country>
<li>Mexique</li>
</country>
</list>
<tree>
<country name="Mexique">
<noRegion>
<name sortKey="Mu Oz Medina, Jose Esteban" sort="Mu Oz Medina, Jose Esteban" uniqKey="Mu Oz Medina J" first="José Esteban" last="Mu Oz-Medina">José Esteban Mu Oz-Medina</name>
</noRegion>
<name sortKey="Angeles Martinez, Javier" sort="Angeles Martinez, Javier" uniqKey="Angeles Martinez J" first="Javier" last="Angeles-Martínez">Javier Angeles-Martínez</name>
<name sortKey="Anguiano Hernandez, Yu Mei" sort="Anguiano Hernandez, Yu Mei" uniqKey="Anguiano Hernandez Y" first="Yu-Mei" last="Anguiano-Hernández">Yu-Mei Anguiano-Hernández</name>
<name sortKey="Diaz Qui Onez, Jose Alberto" sort="Diaz Qui Onez, Jose Alberto" uniqKey="Diaz Qui Onez J" first="José Alberto" last="Díaz-Qui Onez">José Alberto Díaz-Qui Onez</name>
<name sortKey="Diaz Qui Onez, Jose Alberto" sort="Diaz Qui Onez, Jose Alberto" uniqKey="Diaz Qui Onez J" first="José Alberto" last="Díaz-Qui Onez">José Alberto Díaz-Qui Onez</name>
<name sortKey="Gonzalez Bonilla, Cesar Raul" sort="Gonzalez Bonilla, Cesar Raul" uniqKey="Gonzalez Bonilla C" first="César Raúl" last="González-Bonilla">César Raúl González-Bonilla</name>
<name sortKey="Gonzalez Ibarra, Joaquin" sort="Gonzalez Ibarra, Joaquin" uniqKey="Gonzalez Ibarra J" first="Joaquín" last="González-Ibarra">Joaquín González-Ibarra</name>
<name sortKey="Mendez Tenorio, Alfonso" sort="Mendez Tenorio, Alfonso" uniqKey="Mendez Tenorio A" first="Alfonso" last="Méndez-Tenorio">Alfonso Méndez-Tenorio</name>
<name sortKey="Monroy Mu Oz, Irma Eloisa" sort="Monroy Mu Oz, Irma Eloisa" uniqKey="Monroy Mu Oz I" first="Irma Eloísa" last="Monroy-Mu Oz">Irma Eloísa Monroy-Mu Oz</name>
<name sortKey="Ram N Gallegos, Eva" sort="Ram N Gallegos, Eva" uniqKey="Ram N Gallegos E" first="Eva" last="Ram N-Gallegos">Eva Ram N-Gallegos</name>
<name sortKey="Sanchez Vallejo, Carlos Javier" sort="Sanchez Vallejo, Carlos Javier" uniqKey="Sanchez Vallejo C" first="Carlos Javier" last="Sánchez-Vallejo">Carlos Javier Sánchez-Vallejo</name>
<name sortKey="Santacruz Tinoco, Clara Esperanza" sort="Santacruz Tinoco, Clara Esperanza" uniqKey="Santacruz Tinoco C" first="Clara Esperanza" last="Santacruz-Tinoco">Clara Esperanza Santacruz-Tinoco</name>
<name sortKey="Santos Coy Arechavaleta, Andrea" sort="Santos Coy Arechavaleta, Andrea" uniqKey="Santos Coy Arechavaleta A" first="Andrea" last="Santos Coy-Arechavaleta">Andrea Santos Coy-Arechavaleta</name>
</country>
</tree>
</affiliations>
</record>

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