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Prior dengue virus exposure shapes T Cell immunity to Zika Virus in humans
Journal article   Peer reviewed

Prior dengue virus exposure shapes T Cell immunity to Zika Virus in humans

A. Grifoni, J. Pham, J. Sidney, P.H. O'Rourke, S. Paul, B. Peters, S.R. Martini, A.D. de Silva, M.J. Ricciardi, D.M. Magnani, …
Journal of Virology, Vol.91(24)
2017
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Abstract

While progress has been made in characterizing humoral immunity to Zika virus (ZIKV) in humans, little is known regarding the corresponding T cell responses to ZIKV. Here we investigate the kinetics and viral epitopes targeted by T cells responding to ZIKV and address the critical question of whether pre-existing dengue virus (DENV) T cell immunity modulates these responses. We find that memory T cell responses elicited by prior infection with DENV or vaccination with Tetravalent Dengue Attenuated Vaccines (TDLAV) recognize ZIKV-derived peptides. This cross-reactivity is explained by the sequence similarity of the two viruses, as the ZIKV peptides recognized by DENV-elicited memory T cells are identical or highly conserved in DENV and ZIKV. DENV exposure prior to ZIKV infection also influences the timing and magnitude of the T cell response. ZIKV-reactive T cells in the acute phase of infection are detected earlier and in greater magnitude in DENV-immune patients. Conversely, the frequency of ZIKV-reactive T cells continues to rise in the convalescent phase in DENV-naive donors, but declines in DENV pre-exposed donors, compatible with more efficient control of ZIKV replication and/or clearance of ZIKV antigen. The quality of responses is also influenced by previous DENV exposure, and ZIKV-specific CD8 T cells form DENV pre-exposed donors selectively up-regulated granzyme B and PD1, as compared to DENV-naïve donors. Finally, we discovered that ZIKV structural proteins (E, prM and C) are major targets of both the CD4 and CD8 T cell responses, whereas DENV T cell epitopes are found primarily in nonstructural proteins.

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Industry collaboration
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Citation topics
1 Clinical & Life Sciences
1.228 Virology - Tropical Diseases
1.228.200 Mosquito-borne Viruses
Web Of Science research areas
Virology
ESI research areas
Microbiology
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