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Mapping of a dengue virus neutralizing epitope critical for the infectivity of all serotypes: insight into the neutralization mechanism
Laboratoire dIngénierie des Anticorps 1 , Unité de Biochimie Cellulaire 2 and Unité des Arbovirus et Virus des Fièvres Hémorragiques 3 , Institut Pasteur, Paris, France Département de Biologie des Agents Transmissibles, Centre de Recherche du Service de Santé des Armées, BP 87, 38702 La Tronche Ced...
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Published in: | Journal of general virology 2001-08, Vol.82 (8), p.1885-1892 |
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creator | Thullier, Philippe Demangel, Caroline Bedouelle, Hugues Megret, Francoise Jouan, Alain Deubel, Vincent Mazie, Jean-Claude Lafaye, Pierre |
description | Laboratoire dIngénierie des Anticorps 1 , Unité de Biochimie Cellulaire 2 and Unité des Arbovirus et Virus des Fièvres Hémorragiques 3 , Institut Pasteur, Paris, France
Département de Biologie des Agents Transmissibles, Centre de Recherche du Service de Santé des Armées, BP 87, 38702 La Tronche Cedex, France 4
Author for correspondence: Philippe Thullier (at Centre de Recherche du Service de Santé des Armées). Fax +33 4 76 63 69 17. e-mail pthullier{at}yahoo.com
Dengue virus infections are a growing public health concern and strategies to control the spread of the virus are urgently needed. The murine monoclonal antibody 4E11 might be of interest, since it neutralizes dengue viruses of all serotypes by binding to the 296400 segment of the major dengue virus envelope glycoprotein (DE). When phage-displayed peptide libraries were screened by affinity for 4E11, phage clone C1 was selected with a 50% frequency. C1 shared three of nine residues with DE 306314 and showed significant reactivity to 4E11 in ELISA. C1-induced antibodies cross-reacted with DE 296400 in mice, suggesting that it was a structural equivalent of the native epitope of 4E11 on DE. Accordingly, 4E11 bound to the DE 306314 synthetic peptide and this reaction was inhibited by DE 296400 . Moreover, DE 306314 could block dengue virus infection of target cells in an in vitro assay. A three-dimensional model of DE revealed that the three amino acids shared by DE 296400 and C1 were exposed to the solvent and suggested that most of the amino acids comprising the 4E11 epitope were located in the DE 306314 region. Since 4E11 blocked the binding of DE 296400 to heparin, which is a highly sulfated heparan sulfate (HSHS) molecule, 4E11 may act by neutralizing the interaction of DE 306314 with target cell-displayed HSHS. Our data suggest that the DE 306314 segment is critical for the infectivity of all dengue virus serotypes and that molecules that block the binding of DE 306314 to HSHS may be antiviral reagents of therapeutic interest. |
doi_str_mv | 10.1099/0022-1317-82-8-1885 |
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Département de Biologie des Agents Transmissibles, Centre de Recherche du Service de Santé des Armées, BP 87, 38702 La Tronche Cedex, France 4
Author for correspondence: Philippe Thullier (at Centre de Recherche du Service de Santé des Armées). Fax +33 4 76 63 69 17. e-mail pthullier{at}yahoo.com
Dengue virus infections are a growing public health concern and strategies to control the spread of the virus are urgently needed. The murine monoclonal antibody 4E11 might be of interest, since it neutralizes dengue viruses of all serotypes by binding to the 296400 segment of the major dengue virus envelope glycoprotein (DE). When phage-displayed peptide libraries were screened by affinity for 4E11, phage clone C1 was selected with a 50% frequency. C1 shared three of nine residues with DE 306314 and showed significant reactivity to 4E11 in ELISA. C1-induced antibodies cross-reacted with DE 296400 in mice, suggesting that it was a structural equivalent of the native epitope of 4E11 on DE. Accordingly, 4E11 bound to the DE 306314 synthetic peptide and this reaction was inhibited by DE 296400 . Moreover, DE 306314 could block dengue virus infection of target cells in an in vitro assay. A three-dimensional model of DE revealed that the three amino acids shared by DE 296400 and C1 were exposed to the solvent and suggested that most of the amino acids comprising the 4E11 epitope were located in the DE 306314 region. Since 4E11 blocked the binding of DE 296400 to heparin, which is a highly sulfated heparan sulfate (HSHS) molecule, 4E11 may act by neutralizing the interaction of DE 306314 with target cell-displayed HSHS. Our data suggest that the DE 306314 segment is critical for the infectivity of all dengue virus serotypes and that molecules that block the binding of DE 306314 to HSHS may be antiviral reagents of therapeutic interest.</description><identifier>ISSN: 0022-1317</identifier><identifier>EISSN: 1465-2099</identifier><identifier>DOI: 10.1099/0022-1317-82-8-1885</identifier><identifier>PMID: 11457994</identifier><language>eng</language><publisher>England: Soc General Microbiol</publisher><subject>Amino Acid Sequence ; Animals ; Antibodies, Monoclonal - immunology ; Antibodies, Viral - immunology ; Dengue - therapy ; Dengue - virology ; Dengue virus ; Dengue Virus - immunology ; Dengue Virus - pathogenicity ; Epitope Mapping ; Epitopes - analysis ; Glycoproteins - immunology ; Glycoproteins - metabolism ; Heparitin Sulfate - metabolism ; Mice ; Models, Molecular ; Molecular Sequence Data ; Neutralization Tests ; Peptides - chemistry ; Protein Binding ; Species Specificity ; Viral Envelope Proteins - immunology ; Viral Envelope Proteins - metabolism</subject><ispartof>Journal of general virology, 2001-08, Vol.82 (8), p.1885-1892</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c410t-8784c4f89163b0b23d530acb475331aa47f34a31ccb9350dc7b6a0cbd3bbbc273</citedby><cites>FETCH-LOGICAL-c410t-8784c4f89163b0b23d530acb475331aa47f34a31ccb9350dc7b6a0cbd3bbbc273</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11457994$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Thullier, Philippe</creatorcontrib><creatorcontrib>Demangel, Caroline</creatorcontrib><creatorcontrib>Bedouelle, Hugues</creatorcontrib><creatorcontrib>Megret, Francoise</creatorcontrib><creatorcontrib>Jouan, Alain</creatorcontrib><creatorcontrib>Deubel, Vincent</creatorcontrib><creatorcontrib>Mazie, Jean-Claude</creatorcontrib><creatorcontrib>Lafaye, Pierre</creatorcontrib><title>Mapping of a dengue virus neutralizing epitope critical for the infectivity of all serotypes: insight into the neutralization mechanism</title><title>Journal of general virology</title><addtitle>J Gen Virol</addtitle><description>Laboratoire dIngénierie des Anticorps 1 , Unité de Biochimie Cellulaire 2 and Unité des Arbovirus et Virus des Fièvres Hémorragiques 3 , Institut Pasteur, Paris, France
Département de Biologie des Agents Transmissibles, Centre de Recherche du Service de Santé des Armées, BP 87, 38702 La Tronche Cedex, France 4
Author for correspondence: Philippe Thullier (at Centre de Recherche du Service de Santé des Armées). Fax +33 4 76 63 69 17. e-mail pthullier{at}yahoo.com
Dengue virus infections are a growing public health concern and strategies to control the spread of the virus are urgently needed. The murine monoclonal antibody 4E11 might be of interest, since it neutralizes dengue viruses of all serotypes by binding to the 296400 segment of the major dengue virus envelope glycoprotein (DE). When phage-displayed peptide libraries were screened by affinity for 4E11, phage clone C1 was selected with a 50% frequency. C1 shared three of nine residues with DE 306314 and showed significant reactivity to 4E11 in ELISA. C1-induced antibodies cross-reacted with DE 296400 in mice, suggesting that it was a structural equivalent of the native epitope of 4E11 on DE. Accordingly, 4E11 bound to the DE 306314 synthetic peptide and this reaction was inhibited by DE 296400 . Moreover, DE 306314 could block dengue virus infection of target cells in an in vitro assay. A three-dimensional model of DE revealed that the three amino acids shared by DE 296400 and C1 were exposed to the solvent and suggested that most of the amino acids comprising the 4E11 epitope were located in the DE 306314 region. Since 4E11 blocked the binding of DE 296400 to heparin, which is a highly sulfated heparan sulfate (HSHS) molecule, 4E11 may act by neutralizing the interaction of DE 306314 with target cell-displayed HSHS. Our data suggest that the DE 306314 segment is critical for the infectivity of all dengue virus serotypes and that molecules that block the binding of DE 306314 to HSHS may be antiviral reagents of therapeutic interest.</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Antibodies, Monoclonal - immunology</subject><subject>Antibodies, Viral - immunology</subject><subject>Dengue - therapy</subject><subject>Dengue - virology</subject><subject>Dengue virus</subject><subject>Dengue Virus - immunology</subject><subject>Dengue Virus - pathogenicity</subject><subject>Epitope Mapping</subject><subject>Epitopes - analysis</subject><subject>Glycoproteins - immunology</subject><subject>Glycoproteins - metabolism</subject><subject>Heparitin Sulfate - metabolism</subject><subject>Mice</subject><subject>Models, Molecular</subject><subject>Molecular Sequence Data</subject><subject>Neutralization Tests</subject><subject>Peptides - chemistry</subject><subject>Protein Binding</subject><subject>Species Specificity</subject><subject>Viral Envelope Proteins - immunology</subject><subject>Viral Envelope Proteins - metabolism</subject><issn>0022-1317</issn><issn>1465-2099</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><recordid>eNqFkc1O3DAUha2qqExpn6AS8qrqJq3_MnbYIdQ_CcQG1pbt3My4SuJgO6DhBXjtOswIlqzO4nz3WPKH0BdKvlPSND8IYayinMpKsUpVVKn6HVpRsa4rVvr3aPVCHKOPKf0jhApRyw_omNKSTSNW6OnKTJMfNzh02OAWxs0M-N7HOeER5hxN7x-XGiafwwTYRZ-9Mz3uQsR5C9iPHbjs733ePW_0PU4QQ95NkM5Km_xmm0vm8Iy_jJrsw4gHcFsz-jR8Qked6RN8PuQJuv318-biT3V5_fvvxfll5QQluVJSCSc61dA1t8Qy3tacGGeFrDmnxgjZcWE4dc42vCatk3ZtiLMtt9Y6JvkJ-rrfnWK4myFlPfjkoO_NCGFOWlJC1orzN0EqG1azZgH5HnQxpBSh01P0g4k7TYleROlFg140aMW00ouocnV6mJ_tAO3rzcFMAb7tgW35wAcfQW9gHHx5xPqgi6HXrf9O5p-o</recordid><startdate>20010801</startdate><enddate>20010801</enddate><creator>Thullier, Philippe</creator><creator>Demangel, Caroline</creator><creator>Bedouelle, Hugues</creator><creator>Megret, Francoise</creator><creator>Jouan, Alain</creator><creator>Deubel, Vincent</creator><creator>Mazie, Jean-Claude</creator><creator>Lafaye, Pierre</creator><general>Soc General Microbiol</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7U9</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20010801</creationdate><title>Mapping of a dengue virus neutralizing epitope critical for the infectivity of all serotypes: insight into the neutralization mechanism</title><author>Thullier, Philippe ; Demangel, Caroline ; Bedouelle, Hugues ; Megret, Francoise ; Jouan, Alain ; Deubel, Vincent ; Mazie, Jean-Claude ; Lafaye, Pierre</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c410t-8784c4f89163b0b23d530acb475331aa47f34a31ccb9350dc7b6a0cbd3bbbc273</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Antibodies, Monoclonal - immunology</topic><topic>Antibodies, Viral - immunology</topic><topic>Dengue - therapy</topic><topic>Dengue - virology</topic><topic>Dengue virus</topic><topic>Dengue Virus - immunology</topic><topic>Dengue Virus - pathogenicity</topic><topic>Epitope Mapping</topic><topic>Epitopes - analysis</topic><topic>Glycoproteins - immunology</topic><topic>Glycoproteins - metabolism</topic><topic>Heparitin Sulfate - metabolism</topic><topic>Mice</topic><topic>Models, Molecular</topic><topic>Molecular Sequence Data</topic><topic>Neutralization Tests</topic><topic>Peptides - chemistry</topic><topic>Protein Binding</topic><topic>Species Specificity</topic><topic>Viral Envelope Proteins - immunology</topic><topic>Viral Envelope Proteins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Thullier, Philippe</creatorcontrib><creatorcontrib>Demangel, Caroline</creatorcontrib><creatorcontrib>Bedouelle, Hugues</creatorcontrib><creatorcontrib>Megret, Francoise</creatorcontrib><creatorcontrib>Jouan, Alain</creatorcontrib><creatorcontrib>Deubel, Vincent</creatorcontrib><creatorcontrib>Mazie, Jean-Claude</creatorcontrib><creatorcontrib>Lafaye, Pierre</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of general virology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Thullier, Philippe</au><au>Demangel, Caroline</au><au>Bedouelle, Hugues</au><au>Megret, Francoise</au><au>Jouan, Alain</au><au>Deubel, Vincent</au><au>Mazie, Jean-Claude</au><au>Lafaye, Pierre</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mapping of a dengue virus neutralizing epitope critical for the infectivity of all serotypes: insight into the neutralization mechanism</atitle><jtitle>Journal of general virology</jtitle><addtitle>J Gen Virol</addtitle><date>2001-08-01</date><risdate>2001</risdate><volume>82</volume><issue>8</issue><spage>1885</spage><epage>1892</epage><pages>1885-1892</pages><issn>0022-1317</issn><eissn>1465-2099</eissn><abstract>Laboratoire dIngénierie des Anticorps 1 , Unité de Biochimie Cellulaire 2 and Unité des Arbovirus et Virus des Fièvres Hémorragiques 3 , Institut Pasteur, Paris, France
Département de Biologie des Agents Transmissibles, Centre de Recherche du Service de Santé des Armées, BP 87, 38702 La Tronche Cedex, France 4
Author for correspondence: Philippe Thullier (at Centre de Recherche du Service de Santé des Armées). Fax +33 4 76 63 69 17. e-mail pthullier{at}yahoo.com
Dengue virus infections are a growing public health concern and strategies to control the spread of the virus are urgently needed. The murine monoclonal antibody 4E11 might be of interest, since it neutralizes dengue viruses of all serotypes by binding to the 296400 segment of the major dengue virus envelope glycoprotein (DE). When phage-displayed peptide libraries were screened by affinity for 4E11, phage clone C1 was selected with a 50% frequency. C1 shared three of nine residues with DE 306314 and showed significant reactivity to 4E11 in ELISA. C1-induced antibodies cross-reacted with DE 296400 in mice, suggesting that it was a structural equivalent of the native epitope of 4E11 on DE. Accordingly, 4E11 bound to the DE 306314 synthetic peptide and this reaction was inhibited by DE 296400 . Moreover, DE 306314 could block dengue virus infection of target cells in an in vitro assay. A three-dimensional model of DE revealed that the three amino acids shared by DE 296400 and C1 were exposed to the solvent and suggested that most of the amino acids comprising the 4E11 epitope were located in the DE 306314 region. Since 4E11 blocked the binding of DE 296400 to heparin, which is a highly sulfated heparan sulfate (HSHS) molecule, 4E11 may act by neutralizing the interaction of DE 306314 with target cell-displayed HSHS. Our data suggest that the DE 306314 segment is critical for the infectivity of all dengue virus serotypes and that molecules that block the binding of DE 306314 to HSHS may be antiviral reagents of therapeutic interest.</abstract><cop>England</cop><pub>Soc General Microbiol</pub><pmid>11457994</pmid><doi>10.1099/0022-1317-82-8-1885</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Amino Acid Sequence Animals Antibodies, Monoclonal - immunology Antibodies, Viral - immunology Dengue - therapy Dengue - virology Dengue virus Dengue Virus - immunology Dengue Virus - pathogenicity Epitope Mapping Epitopes - analysis Glycoproteins - immunology Glycoproteins - metabolism Heparitin Sulfate - metabolism Mice Models, Molecular Molecular Sequence Data Neutralization Tests Peptides - chemistry Protein Binding Species Specificity Viral Envelope Proteins - immunology Viral Envelope Proteins - metabolism |
title | Mapping of a dengue virus neutralizing epitope critical for the infectivity of all serotypes: insight into the neutralization mechanism |
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