Cross-reactivity and anti-viral function of dengue capsid and NS3-specific memory t cells toward Zika virus
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 diminish...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Frontiers Media
2018
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| _version_ | 1826257453966163968 |
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| author | Lim, M Kumaran, E Tan, H Lye, D Leo, Y Ooi, E Macary, P Bertoletti, A Rivino, L |
| author_facet | Lim, M Kumaran, E Tan, H Lye, D Leo, Y Ooi, E Macary, P Bertoletti, A Rivino, L |
| author_sort | Lim, M |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T18:18:28Z |
| format | Journal article |
| id | oxford-uuid:0572f8c2-9681-48a5-a564-6f30d332694e |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:18:28Z |
| publishDate | 2018 |
| publisher | Frontiers Media |
| record_format | dspace |
| spelling | oxford-uuid:0572f8c2-9681-48a5-a564-6f30d332694e2022-03-26T08:57:17ZCross-reactivity and anti-viral function of dengue capsid and NS3-specific memory t cells toward Zika virusJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:0572f8c2-9681-48a5-a564-6f30d332694eEnglishSymplectic Elements at OxfordFrontiers Media2018Lim, MKumaran, ETan, HLye, DLeo, YOoi, EMacary, PBertoletti, ARivino, LZika 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. |
| spellingShingle | Lim, M Kumaran, E Tan, H Lye, D Leo, Y Ooi, E Macary, P Bertoletti, A Rivino, L Cross-reactivity and anti-viral function of dengue capsid and NS3-specific memory t cells toward Zika virus |
| title | Cross-reactivity and anti-viral function of dengue capsid and NS3-specific memory t cells toward Zika virus |
| title_full | Cross-reactivity and anti-viral function of dengue capsid and NS3-specific memory t cells toward Zika virus |
| title_fullStr | Cross-reactivity and anti-viral function of dengue capsid and NS3-specific memory t cells toward Zika virus |
| title_full_unstemmed | Cross-reactivity and anti-viral function of dengue capsid and NS3-specific memory t cells toward Zika virus |
| title_short | Cross-reactivity and anti-viral function of dengue capsid and NS3-specific memory t cells toward Zika virus |
| title_sort | cross reactivity and anti viral function of dengue capsid and ns3 specific memory t cells toward zika virus |
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