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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2019
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| Online Access: | https://hdl.handle.net/10356/103398 http://hdl.handle.net/10220/47310 |
| _version_ | 1826124466184257536 |
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| author | Lye, David Chienboon Lim, Mei Qiu Kumaran, Emmanuelle A. P. Tan, Hwee Cheng Leo, Yee Sin Ooi, Eng Eong MacAry, Paul A. Bertoletti, Antonio Rivino, Laura |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) Lye, David Chienboon Lim, Mei Qiu Kumaran, Emmanuelle A. P. Tan, Hwee Cheng Leo, Yee Sin Ooi, Eng Eong MacAry, Paul A. Bertoletti, Antonio Rivino, Laura |
| author_sort | Lye, David Chienboon |
| collection | NTU |
| 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 | 2024-10-01T06:20:46Z |
| format | Journal Article |
| id | ntu-10356/103398 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T06:20:46Z |
| publishDate | 2019 |
| record_format | dspace |
| spelling | ntu-10356/1033982020-11-01T05:23:26Z Cross-reactivity and anti-viral function of dengue capsid and NS3-specific memory T cells toward Zika virus Lye, David Chienboon Lim, Mei Qiu Kumaran, Emmanuelle A. P. Tan, Hwee Cheng Leo, Yee Sin Ooi, Eng Eong MacAry, Paul A. Bertoletti, Antonio Rivino, Laura Lee Kong Chian School of Medicine (LKCMedicine) Zika Virus (ZIKV) Dengue Virus (DENV) DRNTU::Science::Medicine 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. NMRC (Natl Medical Research Council, S’pore) Published version 2019-01-02T07:04:18Z 2019-12-06T21:11:46Z 2019-01-02T07:04:18Z 2019-12-06T21:11:46Z 2018 Journal Article Lim, 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.2018.02225 https://hdl.handle.net/10356/103398 http://hdl.handle.net/10220/47310 10.3389/fimmu.2018.02225 en Frontiers in Immunology © 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. 14 p. application/pdf |
| spellingShingle | Zika Virus (ZIKV) Dengue Virus (DENV) DRNTU::Science::Medicine Lye, David Chienboon Lim, Mei Qiu Kumaran, Emmanuelle A. P. Tan, Hwee Cheng Leo, Yee Sin Ooi, Eng Eong MacAry, Paul A. Bertoletti, Antonio Rivino, Laura 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 |
| topic | Zika Virus (ZIKV) Dengue Virus (DENV) DRNTU::Science::Medicine |
| url | https://hdl.handle.net/10356/103398 http://hdl.handle.net/10220/47310 |
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