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dc.contributor.authorLye, David Chienboonen
dc.contributor.authorLim, Mei Qiuen
dc.contributor.authorKumaran, Emmanuelle A. P.en
dc.contributor.authorTan, Hwee Chengen
dc.contributor.authorLeo, Yee Sinen
dc.contributor.authorOoi, Eng Eongen
dc.contributor.authorMacAry, Paul A.en
dc.contributor.authorBertoletti, Antonioen
dc.contributor.authorRivino, Lauraen
dc.identifier.citationLim, M. Q., Kumaran, E. A. P., Tan, H. C., Lye, D. C., Leo, Y. S., Ooi, E. E., . . . 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, 2225-. doi:10.3389/fimmu.2018.02225en
dc.description.abstractZika 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.en
dc.description.sponsorshipNMRC (Natl Medical Research Council, S’pore)en
dc.format.extent14 p.en
dc.relation.ispartofseriesFrontiers in Immunologyen
dc.rights© 2018 Lim, Kumaran, Tan, Lye, Leo, Ooi, MacAry, Bertoletti and Rivino. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.en
dc.subjectZika Virus (ZIKV)en
dc.subjectDengue Virus (DENV)en
dc.titleCross-reactivity and anti-viral function of dengue capsid and NS3-specific memory T cells toward Zika virusen
dc.typeJournal Articleen
dc.contributor.schoolLee Kong Chian School of Medicine (LKCMedicine)en
dc.description.versionPublished versionen
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