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T cell immunity to Zika virus targets immunodominant epitopes that show cross-reactivity with other Flaviviruses

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Title: T cell immunity to Zika virus targets immunodominant epitopes that show cross-reactivity with other Flaviviruses
Authors: Reynolds, CJ
Suleyman, OM
Ortega-Prieto, AM
Skelton, JK
Bonnesoeur, P
Blohm, A
Carregaro, V
Silva, JS
James, EA
Maillere, B
Dorner, M
Boyton, RJ
Altmann, DM
Item Type: Journal Article
Abstract: Zika virus (ZIKV) Infection has several outcomes from asymptomatic exposure to rash, conjunctivitis, Guillain-Barré syndrome or congenital Zika syndrome. Analysis of ZIKV immunity is confounded by the fact that several related Flaviviruses infect humans, including Dengue virus 1–4, West Nile virus and Yellow Fever virus. HLA class II restricted T cell cross-reactivity between ZIKV and other Flaviviruses infection(s) or vaccination may contribute to protection or to enhanced immunopathology. We mapped immunodominant, HLA class II restricted, CD4 epitopes from ZIKV Envelope (Env), and Non-structural (NS) NS1, NS3 and NS5 antigens in HLA class II transgenic mice. In several cases, ZIKV primed CD4 cells responded to homologous sequences from other viruses, including DENV1–4, WNV or YFV. However, cross-reactive responses could confer immune deviation - the response to the Env DENV4 p1 epitope in HLA-DR1 resulted in IL-17A immunity, often associated with exacerbated immunopathogenesis. This conservation of recognition across Flaviviruses, may encompass protective and/or pathogenic components and poses challenges to characterization of ZIKV protective immunity.
Issue Date: 12-Jan-2018
Date of Acceptance: 18-Dec-2017
URI: http://hdl.handle.net/10044/1/55342
DOI: https://dx.doi.org/10.1038/s41598-017-18781-1
ISSN: 2045-2322
Publisher: Nature Publishing Group
Journal / Book Title: Scientific Reports
Volume: 8
Copyright Statement: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Te images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. © The Author(s) 2017
Sponsor/Funder: Wellcome Trust
European Research Council
Commission of the European Communities
Medical Research Council (MRC)
Medical Research Council
National Institutes of Health
Funder's Grant Number: 104771/Z/14/Z
637304
MC_PC_15106
MC_PC_15106
BPO: 20151; UWSC9568
Publication Status: Published
Article Number: 672
Appears in Collections:Department of Medicine (up to 2019)