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Alanine Substitution Inactivates Cross-Reacting Epitopes in Dengue Virus Recombinant Envelope Proteins

The expansion of the habitat of mosquitoes belonging to the Aedes genus puts nearly half of the world’s population at risk of contracting dengue fever, and a significant fraction will develop its serious hemorrhagic complication, which can be fatal if not diagnosed properly and treated in a timely f...

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Autores principales: Zomosa-Signoret, Viviana C., Morales-González, Karina R., Estrada-Rodríguez, Ana E., Rivas-Estilla, Ana M., Devèze-García, M. Cristina, Galaviz-Aguilar, Edgar, Vidaltamayo, Román
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7077257/
https://www.ncbi.nlm.nih.gov/pubmed/32069839
http://dx.doi.org/10.3390/v12020208
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author Zomosa-Signoret, Viviana C.
Morales-González, Karina R.
Estrada-Rodríguez, Ana E.
Rivas-Estilla, Ana M.
Devèze-García, M. Cristina
Galaviz-Aguilar, Edgar
Vidaltamayo, Román
author_facet Zomosa-Signoret, Viviana C.
Morales-González, Karina R.
Estrada-Rodríguez, Ana E.
Rivas-Estilla, Ana M.
Devèze-García, M. Cristina
Galaviz-Aguilar, Edgar
Vidaltamayo, Román
author_sort Zomosa-Signoret, Viviana C.
collection PubMed
description The expansion of the habitat of mosquitoes belonging to the Aedes genus puts nearly half of the world’s population at risk of contracting dengue fever, and a significant fraction will develop its serious hemorrhagic complication, which can be fatal if not diagnosed properly and treated in a timely fashion. Although several diagnostic methods have been approved for dengue diagnostics, their applicability is limited in rural areas of developing countries by sample preparation costs and methodological requirements, as well as cross-reactivity among the different serotypes of the Dengue virus and other flavivirus, such as the Zika virus. For these reasons, it is necessary to generate more specific antigens to improve serological methods that could be cheaper and used in field operations. Here, we describe a strategy for the inactivation of cross-reacting epitopes on the surface of the Dengue virus envelope protein through the synthetic generation of recombinant peptide sequences, where key amino acid residues from Dengue virus serotype 1 (DENV-1) and 2 (DENV-2) are substituted by alanine residues. The proteins thus generated are recognized by 88% of sera from Dengue NS1+ patients and show improved serotype specificity because they do not react with the antibodies present in seroconverted, PCR-serotyped DEN-4 infected patients.
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spelling pubmed-70772572020-03-20 Alanine Substitution Inactivates Cross-Reacting Epitopes in Dengue Virus Recombinant Envelope Proteins Zomosa-Signoret, Viviana C. Morales-González, Karina R. Estrada-Rodríguez, Ana E. Rivas-Estilla, Ana M. Devèze-García, M. Cristina Galaviz-Aguilar, Edgar Vidaltamayo, Román Viruses Article The expansion of the habitat of mosquitoes belonging to the Aedes genus puts nearly half of the world’s population at risk of contracting dengue fever, and a significant fraction will develop its serious hemorrhagic complication, which can be fatal if not diagnosed properly and treated in a timely fashion. Although several diagnostic methods have been approved for dengue diagnostics, their applicability is limited in rural areas of developing countries by sample preparation costs and methodological requirements, as well as cross-reactivity among the different serotypes of the Dengue virus and other flavivirus, such as the Zika virus. For these reasons, it is necessary to generate more specific antigens to improve serological methods that could be cheaper and used in field operations. Here, we describe a strategy for the inactivation of cross-reacting epitopes on the surface of the Dengue virus envelope protein through the synthetic generation of recombinant peptide sequences, where key amino acid residues from Dengue virus serotype 1 (DENV-1) and 2 (DENV-2) are substituted by alanine residues. The proteins thus generated are recognized by 88% of sera from Dengue NS1+ patients and show improved serotype specificity because they do not react with the antibodies present in seroconverted, PCR-serotyped DEN-4 infected patients. MDPI 2020-02-13 /pmc/articles/PMC7077257/ /pubmed/32069839 http://dx.doi.org/10.3390/v12020208 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zomosa-Signoret, Viviana C.
Morales-González, Karina R.
Estrada-Rodríguez, Ana E.
Rivas-Estilla, Ana M.
Devèze-García, M. Cristina
Galaviz-Aguilar, Edgar
Vidaltamayo, Román
Alanine Substitution Inactivates Cross-Reacting Epitopes in Dengue Virus Recombinant Envelope Proteins
title Alanine Substitution Inactivates Cross-Reacting Epitopes in Dengue Virus Recombinant Envelope Proteins
title_full Alanine Substitution Inactivates Cross-Reacting Epitopes in Dengue Virus Recombinant Envelope Proteins
title_fullStr Alanine Substitution Inactivates Cross-Reacting Epitopes in Dengue Virus Recombinant Envelope Proteins
title_full_unstemmed Alanine Substitution Inactivates Cross-Reacting Epitopes in Dengue Virus Recombinant Envelope Proteins
title_short Alanine Substitution Inactivates Cross-Reacting Epitopes in Dengue Virus Recombinant Envelope Proteins
title_sort alanine substitution inactivates cross-reacting epitopes in dengue virus recombinant envelope proteins
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7077257/
https://www.ncbi.nlm.nih.gov/pubmed/32069839
http://dx.doi.org/10.3390/v12020208
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