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Analysis of the T Cell Response to Zika Virus and Identification of a Novel CD8(+) T Cell Epitope in Immunocompetent Mice

Zika virus (ZIKV) is an emerging arbovirus of the Flaviviridae family. Although ZIKV infection is typically mild and self-limiting in healthy adults, infection has been associated with neurological symptoms such as Guillain-Barré syndrome, and a causal link has been established between fetal microce...

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Autores principales: Pardy, Ryan D., Rajah, Maaran M., Condotta, Stephanie A., Taylor, Nathan G., Sagan, Selena M., Richer, Martin J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5322871/
https://www.ncbi.nlm.nih.gov/pubmed/28231312
http://dx.doi.org/10.1371/journal.ppat.1006184
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author Pardy, Ryan D.
Rajah, Maaran M.
Condotta, Stephanie A.
Taylor, Nathan G.
Sagan, Selena M.
Richer, Martin J.
author_facet Pardy, Ryan D.
Rajah, Maaran M.
Condotta, Stephanie A.
Taylor, Nathan G.
Sagan, Selena M.
Richer, Martin J.
author_sort Pardy, Ryan D.
collection PubMed
description Zika virus (ZIKV) is an emerging arbovirus of the Flaviviridae family. Although ZIKV infection is typically mild and self-limiting in healthy adults, infection has been associated with neurological symptoms such as Guillain-Barré syndrome, and a causal link has been established between fetal microcephaly and ZIKV infection during pregnancy. These risks, and the magnitude of the ongoing ZIKV pandemic, have created an urgent need for the development of animal models to study the immune response to ZIKV infection. Previous animal models have primarily focused on pathogenesis in immunocompromised mice. In this study, we provide a model of ZIKV infection in wild-type immunocompetent C57BL/6 mice, and have provided an analysis of the immune response to infection. We evaluated the activation of several innate immune cell types, and studied the kinetics, phenotype, and functionality of T cell responses to ZIKV infection. Our results demonstrate that ZIKV infection is mild in wild-type immunocompetent C57BL/6 mice, resulting in minimal morbidity. Our data establish that at the peak of the adaptive response, antigen-experienced CD4(+) T cells polarize to a Th1 phenotype, and antigen-experienced CD8(+) T cells exhibit an activated effector phenotype, producing both effector cytokines and cytolytic molecules. Furthermore, we have identified a novel ZIKV CD8(+) T cell epitope in the envelope protein that is recognized by the majority of responding cells. Our model provides an important reference point that will help dissect the impact of polymorphisms in the circulating ZIKV strains on the immune response and ZIKV pathogenesis. In addition, the identification of a ZIKV epitope will allow for the design of tetramers to study epitope-specific T cell responses, and will have important implications for the design and development of ZIKV vaccine strategies.
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spelling pubmed-53228712017-03-09 Analysis of the T Cell Response to Zika Virus and Identification of a Novel CD8(+) T Cell Epitope in Immunocompetent Mice Pardy, Ryan D. Rajah, Maaran M. Condotta, Stephanie A. Taylor, Nathan G. Sagan, Selena M. Richer, Martin J. PLoS Pathog Research Article Zika virus (ZIKV) is an emerging arbovirus of the Flaviviridae family. Although ZIKV infection is typically mild and self-limiting in healthy adults, infection has been associated with neurological symptoms such as Guillain-Barré syndrome, and a causal link has been established between fetal microcephaly and ZIKV infection during pregnancy. These risks, and the magnitude of the ongoing ZIKV pandemic, have created an urgent need for the development of animal models to study the immune response to ZIKV infection. Previous animal models have primarily focused on pathogenesis in immunocompromised mice. In this study, we provide a model of ZIKV infection in wild-type immunocompetent C57BL/6 mice, and have provided an analysis of the immune response to infection. We evaluated the activation of several innate immune cell types, and studied the kinetics, phenotype, and functionality of T cell responses to ZIKV infection. Our results demonstrate that ZIKV infection is mild in wild-type immunocompetent C57BL/6 mice, resulting in minimal morbidity. Our data establish that at the peak of the adaptive response, antigen-experienced CD4(+) T cells polarize to a Th1 phenotype, and antigen-experienced CD8(+) T cells exhibit an activated effector phenotype, producing both effector cytokines and cytolytic molecules. Furthermore, we have identified a novel ZIKV CD8(+) T cell epitope in the envelope protein that is recognized by the majority of responding cells. Our model provides an important reference point that will help dissect the impact of polymorphisms in the circulating ZIKV strains on the immune response and ZIKV pathogenesis. In addition, the identification of a ZIKV epitope will allow for the design of tetramers to study epitope-specific T cell responses, and will have important implications for the design and development of ZIKV vaccine strategies. Public Library of Science 2017-02-23 /pmc/articles/PMC5322871/ /pubmed/28231312 http://dx.doi.org/10.1371/journal.ppat.1006184 Text en © 2017 Pardy et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Pardy, Ryan D.
Rajah, Maaran M.
Condotta, Stephanie A.
Taylor, Nathan G.
Sagan, Selena M.
Richer, Martin J.
Analysis of the T Cell Response to Zika Virus and Identification of a Novel CD8(+) T Cell Epitope in Immunocompetent Mice
title Analysis of the T Cell Response to Zika Virus and Identification of a Novel CD8(+) T Cell Epitope in Immunocompetent Mice
title_full Analysis of the T Cell Response to Zika Virus and Identification of a Novel CD8(+) T Cell Epitope in Immunocompetent Mice
title_fullStr Analysis of the T Cell Response to Zika Virus and Identification of a Novel CD8(+) T Cell Epitope in Immunocompetent Mice
title_full_unstemmed Analysis of the T Cell Response to Zika Virus and Identification of a Novel CD8(+) T Cell Epitope in Immunocompetent Mice
title_short Analysis of the T Cell Response to Zika Virus and Identification of a Novel CD8(+) T Cell Epitope in Immunocompetent Mice
title_sort analysis of the t cell response to zika virus and identification of a novel cd8(+) t cell epitope in immunocompetent mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5322871/
https://www.ncbi.nlm.nih.gov/pubmed/28231312
http://dx.doi.org/10.1371/journal.ppat.1006184
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