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Title: Cross-reactivity and anti-viral function of dengue capsid and NS3- specific memory t cells toward Zika Virus
Authors: Lim, M.Q. 
Kumaran, E.A.P. 
Tan, H.C. 
Lye, D.C. 
Leo, Y.S. 
Ooi, E.E. 
MacAry, P.A. 
Bertoletti, A. 
Rivino, L. 
Keywords: cytokine
NS3 protein, flavivirus
RNA helicase
serine proteinase
viral protein
CD4+ T lymphocyte
CD8+ T lymphocyte
cell culture
cross reaction
Dengue virus
heterologous immunity
immunological memory
virus capsid
Zika fever
Zika virus
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Cells, Cultured
Cross Reactions
Dengue Virus
Epitopes, T-Lymphocyte
Immunity, Heterologous
Immunologic Memory
RNA Helicases
Serine Endopeptidases
Viral Nonstructural Proteins
Zika Virus
Zika Virus Infection
Issue Date: 2018
Publisher: Frontiers Media S.A.
Citation: Lim, M.Q., Kumaran, E.A.P., Tan, H.C., Lye, D.C., Leo, Y.S., Ooi, E.E., MacAry, P.A., Bertoletti, A., Rivino, L. (2018). Cross-reactivity and anti-viral function of dengue capsid and NS3- specific memory t cells toward Zika Virus. Frontiers in Immunology 9 (OCT) : 2225. ScholarBank@NUS Repository.
Abstract: Zika virus (ZIKV), a flavivirus with homology to dengue virus (DENV), is spreading to areas of DENV hyper-endemicity. Heterologous T cell immunity, whereby virus-specific memory T cells are activated by variant peptides derived from a different virus, can lead to enhanced viral clearance or diminished protective immunity and altered immunopathology. In mice, CD8+ T cells specific for DENV provide in vivo protective efficacy against subsequent ZIKV infection. In humans, contrasting studies report complete absence or varying degrees of DENV/ZIKV T cell cross-reactivity. Moreover, the impact of cross-reactive T cell recognition on the anti-viral capacity of T cells remains unclear. Here, we show that DENV-specific memory T cells display robust cross-reactive recognition of ZIKV NS3 ex vivo and after in vitro expansion in respectively n = 7/10 and n = 9/9 dengue-immune individuals tested. In contrast, cross-reactivity toward ZIKV capsid is low or absent. Cross-reactive recognition of DENV or ZIKV NS3 peptides elicits similar production of the anti-viral effector mediators IFN-γ, TNF-α, and CD107a. We identify 9 DENV/ZIKV cross-reactive epitopes, 7 of which are CD4+ and 2 are CD8+ T cell epitopes. We also show that cross-reactive CD4+ and CD8+ T cells targeting novel NS3 epitopes display anti-viral effector potential toward ZIKV-infected cells, with CD8+ T cells mediating direct lyses of these cells. Our results demonstrate that DENV NS3-specific memory T cells display anti-viral effector capacity toward ZIKV, suggesting a potential beneficial effect in humans of pre-existing T cell immunity to DENV upon ZIKV infection. © 2018 Lim, Kumaran, Tan, Lye, Leo, Ooi, MacAry, Bertoletti and Rivino.
Source Title: Frontiers in Immunology
ISSN: 16643224
DOI: 10.3389/fimmu.2018.02225
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