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West Nile Virus T-Cell Ligand Sequences Shared with Other Flaviviruses: a Multitude of Variant Sequences as Potential Altered Peptide Ligands

Identifieur interne : 000540 ( France/Analysis ); précédent : 000539; suivant : 000541

West Nile Virus T-Cell Ligand Sequences Shared with Other Flaviviruses: a Multitude of Variant Sequences as Potential Altered Peptide Ligands

Auteurs : Keun-Ok Jung [États-Unis] ; Asif M. Khan [États-Unis, Malaisie, Singapour] ; Benjamin Yong Liang Tan [Singapour] ; YONGLI HU [Malaisie, Singapour] ; Gregory G. Simon [États-Unis] ; Eduardo J. M. Nascimento [États-Unis] ; Francois Lemonnier [France] ; Vladimir Brusic [États-Unis] ; Olivo Miotto [Thaïlande] ; TIN WEE TAN [Singapour] ; Ernesto T. A. Marques [États-Unis, Brésil] ; Rafael Dhalia [Brésil] ; Jerome Salmon [États-Unis, France] ; J. Thomas August [États-Unis, Malaisie]

Source :

RBID : Pascal:12-0288204

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English descriptors

Abstract

Phylogenetic relatedness and cocirculation of several major human pathogen flaviviruses are recognized as a possible cause of deleterious immune responses to mixed infection or immunization and call for a greater understanding of the inter-Flavivirus protein homologies. This study focused on the identification of human leukocyte antigen (HLA)-restricted West Nile virus (WNV) T-cell ligands and characterization of their distribution in reported sequence data of WNV and other flaviviruses. H-2-deficient mice transgenic for either A2, A24, B7, DR2, DR3, or DR4 HLA alleles were immunized with overlapping peptides of the WNV proteome, and peptide-specific T-cell activation was measured by gamma interferon (IFN-γ) enzyme-linked immunosorbent spot (ELISpot) assays. Approximately 30% (137) of the WNV proteome peptides were identified as HLA-restricted T-cell ligands. The majority of these ligands were conserved in ∼≥88% of analyzed WNV sequences. Notably, only 51 were WNV specific, and the remaining 86, chiefly of E, NS3, and NS5, shared an identity of nine or more consecutive amino acids with sequences of 64 other flaviviruses, including several major human pathogens. Many of the shared ligands had an incidence of > 50% in the analyzed sequences of one or more of six major flaviviruses. The multitude of WNV sequences shared with other flaviviruses as interspecies variants highlights the possible hazard of defective T-cell activation by altered peptide ligands in the event of dual exposure to WNV and other flaviviruses, by either infection or immunization. The data suggest the possible preferred use of sequences that are pathogen specific with minimum interspecies sequence homology for the design of Flavivirus vaccines.


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Pascal:12-0288204

Le document en format XML

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<author>
<name sortKey="Miotto, Olivo" sort="Miotto, Olivo" uniqKey="Miotto O" first="Olivo" last="Miotto">Olivo Miotto</name>
<affiliation wicri:level="1">
<inist:fA14 i1="07">
<s1>Mahidol-Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University</s1>
<s2>Bangkok</s2>
<s3>THA</s3>
<sZ>9 aut.</sZ>
</inist:fA14>
<country>Thaïlande</country>
<wicri:noRegion>Bangkok</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Tin Wee Tan" sort="Tin Wee Tan" uniqKey="Tin Wee Tan" last="Tin Wee Tan">TIN WEE TAN</name>
<affiliation wicri:level="4">
<inist:fA14 i1="03">
<s1>Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore</s1>
<s2>Singapore</s2>
<s3>SGP</s3>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>10 aut.</sZ>
</inist:fA14>
<country>Singapour</country>
<orgName type="university">Université nationale de Singapour</orgName>
</affiliation>
</author>
<author>
<name sortKey="Marques, Ernesto T A" sort="Marques, Ernesto T A" uniqKey="Marques E" first="Ernesto T. A." last="Marques">Ernesto T. A. Marques</name>
<affiliation wicri:level="4">
<inist:fA14 i1="04">
<s1>Center for Vaccine Research, University of Pittsburgh</s1>
<s2>Pittsburgh, Pennsylvania</s2>
<s3>USA</s3>
<sZ>6 aut.</sZ>
<sZ>11 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName>
<region type="state">Pennsylvanie</region>
<settlement type="city">Pittsburgh</settlement>
</placeName>
<orgName type="university">Université de Pittsburgh</orgName>
</affiliation>
<affiliation wicri:level="2">
<inist:fA14 i1="08">
<s1>Virology and Experimental Therapy Laboratory, Aggeu Magalhães Research Center</s1>
<s2>Recife, Pernambuco</s2>
<s3>BRA</s3>
<sZ>11 aut.</sZ>
<sZ>12 aut.</sZ>
</inist:fA14>
<country>Brésil</country>
<placeName>
<region type="state">Pernambuco</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Dhalia, Rafael" sort="Dhalia, Rafael" uniqKey="Dhalia R" first="Rafael" last="Dhalia">Rafael Dhalia</name>
<affiliation wicri:level="2">
<inist:fA14 i1="08">
<s1>Virology and Experimental Therapy Laboratory, Aggeu Magalhães Research Center</s1>
<s2>Recife, Pernambuco</s2>
<s3>BRA</s3>
<sZ>11 aut.</sZ>
<sZ>12 aut.</sZ>
</inist:fA14>
<country>Brésil</country>
<placeName>
<region type="state">Pernambuco</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Salmon, Jerome" sort="Salmon, Jerome" uniqKey="Salmon J" first="Jerome" last="Salmon">Jerome Salmon</name>
<affiliation wicri:level="2">
<inist:fA14 i1="01">
<s1>Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine</s1>
<s2>Baltimore, Maryland</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>13 aut.</sZ>
<sZ>14 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName>
<region type="state">Maryland</region>
</placeName>
</affiliation>
<affiliation wicri:level="1">
<inist:fA14 i1="09">
<s1>Unité des Retrovirus Endogènes et Eléments Rétroïdes des Eucaryotes Superieurs, Institut Gustave Roussy</s1>
<s2>Villejuif</s2>
<s3>FRA</s3>
<sZ>13 aut.</sZ>
</inist:fA14>
<country>France</country>
<wicri:noRegion>Villejuif</wicri:noRegion>
<wicri:noRegion>Institut Gustave Roussy</wicri:noRegion>
<wicri:noRegion>Villejuif</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Thomas August, J" sort="Thomas August, J" uniqKey="Thomas August J" first="J." last="Thomas August">J. Thomas August</name>
<affiliation wicri:level="2">
<inist:fA14 i1="01">
<s1>Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine</s1>
<s2>Baltimore, Maryland</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>13 aut.</sZ>
<sZ>14 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName>
<region type="state">Maryland</region>
</placeName>
</affiliation>
<affiliation wicri:level="1">
<inist:fA14 i1="02">
<s1>Perdana University Graduate School of Medicine</s1>
<s2>Serdang, Selangor Darul Ehsan</s2>
<s3>MYS</s3>
<sZ>2 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>14 aut.</sZ>
</inist:fA14>
<country>Malaisie</country>
<wicri:noRegion>Perdana University Graduate School of Medicine</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series>
<title level="j" type="main">Journal of virology</title>
<title level="j" type="abbreviated">J. virol.</title>
<idno type="ISSN">0022-538X</idno>
<imprint>
<date when="2012">2012</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt>
<title level="j" type="main">Journal of virology</title>
<title level="j" type="abbreviated">J. virol.</title>
<idno type="ISSN">0022-538X</idno>
</seriesStmt>
</fileDesc>
<profileDesc>
<textClass>
<keywords scheme="KwdEn" xml:lang="en">
<term>Peptides</term>
<term>T-Lymphocyte</term>
<term>West Nile virus</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr">
<term>Virus West Nile</term>
<term>Lymphocyte T</term>
<term>Peptide</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">Phylogenetic relatedness and cocirculation of several major human pathogen flaviviruses are recognized as a possible cause of deleterious immune responses to mixed infection or immunization and call for a greater understanding of the inter-Flavivirus protein homologies. This study focused on the identification of human leukocyte antigen (HLA)-restricted West Nile virus (WNV) T-cell ligands and characterization of their distribution in reported sequence data of WNV and other flaviviruses. H-2-deficient mice transgenic for either A2, A24, B7, DR2, DR3, or DR4 HLA alleles were immunized with overlapping peptides of the WNV proteome, and peptide-specific T-cell activation was measured by gamma interferon (IFN-γ) enzyme-linked immunosorbent spot (ELISpot) assays. Approximately 30% (137) of the WNV proteome peptides were identified as HLA-restricted T-cell ligands. The majority of these ligands were conserved in ∼≥88% of analyzed WNV sequences. Notably, only 51 were WNV specific, and the remaining 86, chiefly of E, NS3, and NS5, shared an identity of nine or more consecutive amino acids with sequences of 64 other flaviviruses, including several major human pathogens. Many of the shared ligands had an incidence of > 50% in the analyzed sequences of one or more of six major flaviviruses. The multitude of WNV sequences shared with other flaviviruses as interspecies variants highlights the possible hazard of defective T-cell activation by altered peptide ligands in the event of dual exposure to WNV and other flaviviruses, by either infection or immunization. The data suggest the possible preferred use of sequences that are pathogen specific with minimum interspecies sequence homology for the design of Flavivirus vaccines.</div>
</front>
</TEI>
<affiliations>
<list>
<country>
<li>Brésil</li>
<li>France</li>
<li>Malaisie</li>
<li>Singapour</li>
<li>Thaïlande</li>
<li>États-Unis</li>
</country>
<region>
<li>Maryland</li>
<li>Massachusetts</li>
<li>Pennsylvanie</li>
<li>Pernambuco</li>
<li>Île-de-France</li>
</region>
<settlement>
<li>Paris</li>
<li>Pittsburgh</li>
</settlement>
<orgName>
<li>Université de Pittsburgh</li>
<li>Université nationale de Singapour</li>
</orgName>
</list>
<tree>
<country name="États-Unis">
<region name="Maryland">
<name sortKey="Jung, Keun Ok" sort="Jung, Keun Ok" uniqKey="Jung K" first="Keun-Ok" last="Jung">Keun-Ok Jung</name>
</region>
<name sortKey="Brusic, Vladimir" sort="Brusic, Vladimir" uniqKey="Brusic V" first="Vladimir" last="Brusic">Vladimir Brusic</name>
<name sortKey="Khan, Asif M" sort="Khan, Asif M" uniqKey="Khan A" first="Asif M." last="Khan">Asif M. Khan</name>
<name sortKey="Marques, Ernesto T A" sort="Marques, Ernesto T A" uniqKey="Marques E" first="Ernesto T. A." last="Marques">Ernesto T. A. Marques</name>
<name sortKey="Nascimento, Eduardo J M" sort="Nascimento, Eduardo J M" uniqKey="Nascimento E" first="Eduardo J. M." last="Nascimento">Eduardo J. M. Nascimento</name>
<name sortKey="Salmon, Jerome" sort="Salmon, Jerome" uniqKey="Salmon J" first="Jerome" last="Salmon">Jerome Salmon</name>
<name sortKey="Simon, Gregory G" sort="Simon, Gregory G" uniqKey="Simon G" first="Gregory G." last="Simon">Gregory G. Simon</name>
<name sortKey="Thomas August, J" sort="Thomas August, J" uniqKey="Thomas August J" first="J." last="Thomas August">J. Thomas August</name>
</country>
<country name="Malaisie">
<noRegion>
<name sortKey="Khan, Asif M" sort="Khan, Asif M" uniqKey="Khan A" first="Asif M." last="Khan">Asif M. Khan</name>
</noRegion>
<name sortKey="Thomas August, J" sort="Thomas August, J" uniqKey="Thomas August J" first="J." last="Thomas August">J. Thomas August</name>
<name sortKey="Yongli Hu" sort="Yongli Hu" uniqKey="Yongli Hu" last="Yongli Hu">YONGLI HU</name>
</country>
<country name="Singapour">
<noRegion>
<name sortKey="Khan, Asif M" sort="Khan, Asif M" uniqKey="Khan A" first="Asif M." last="Khan">Asif M. Khan</name>
</noRegion>
<name sortKey="Liang Tan, Benjamin Yong" sort="Liang Tan, Benjamin Yong" uniqKey="Liang Tan B" first="Benjamin Yong" last="Liang Tan">Benjamin Yong Liang Tan</name>
<name sortKey="Tin Wee Tan" sort="Tin Wee Tan" uniqKey="Tin Wee Tan" last="Tin Wee Tan">TIN WEE TAN</name>
<name sortKey="Yongli Hu" sort="Yongli Hu" uniqKey="Yongli Hu" last="Yongli Hu">YONGLI HU</name>
</country>
<country name="France">
<region name="Île-de-France">
<name sortKey="Lemonnier, Francois" sort="Lemonnier, Francois" uniqKey="Lemonnier F" first="Francois" last="Lemonnier">Francois Lemonnier</name>
</region>
<name sortKey="Salmon, Jerome" sort="Salmon, Jerome" uniqKey="Salmon J" first="Jerome" last="Salmon">Jerome Salmon</name>
</country>
<country name="Thaïlande">
<noRegion>
<name sortKey="Miotto, Olivo" sort="Miotto, Olivo" uniqKey="Miotto O" first="Olivo" last="Miotto">Olivo Miotto</name>
</noRegion>
</country>
<country name="Brésil">
<region name="Pernambuco">
<name sortKey="Marques, Ernesto T A" sort="Marques, Ernesto T A" uniqKey="Marques E" first="Ernesto T. A." last="Marques">Ernesto T. A. Marques</name>
</region>
<name sortKey="Dhalia, Rafael" sort="Dhalia, Rafael" uniqKey="Dhalia R" first="Rafael" last="Dhalia">Rafael Dhalia</name>
</country>
</tree>
</affiliations>
</record>

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