Journal article
Prior dengue virus exposure shapes T Cell immunity to Zika Virus in humans
Journal of Virology, Vol.91(24)
2017
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.
Details
- Title
- Prior dengue virus exposure shapes T Cell immunity to Zika Virus in humans
- Authors/Creators
- A. Grifoni (Author/Creator) - La Jolla Institute for ImmunologyJ. Pham (Author/Creator) - La Jolla Institute for ImmunologyJ. Sidney (Author/Creator) - La Jolla Institute for ImmunologyP.H. O'Rourke (Author/Creator) - La Jolla Institute for ImmunologyS. Paul (Author/Creator) - La Jolla Institute for ImmunologyB. Peters (Author/Creator) - La Jolla Institute for ImmunologyS.R. Martini (Author/Creator) - La Jolla Institute for ImmunologyA.D. de Silva (Author/Creator)M.J. Ricciardi (Author/Creator) - University of MiamiD.M. Magnani (Author/Creator) - University of MiamiC.G.T. Silveira (Author/Creator) - Universidade de São PauloA. Maestri (Author/Creator) - Universidade de São PauloP.R. Costa (Author/Creator) - Universidade de São PauloL.M. de-Oliveira-Pinto (Author/Creator) - Fundação Oswaldo CruzE.L. de Azeredo (Author/Creator) - Fundação Oswaldo CruzP.V. Damasco (Author/Creator) - Universidade Federal do Estado do Rio de JaneiroE. Phillips (Author/Creator) - Vanderbilt UniversityS. Mallal (Author/Creator) - Vanderbilt UniversityA.M. de Silva (Author/Creator) - La Jolla Institute for ImmunologyM. Collins (Author/Creator) - University of North Carolina at Chapel HillA. Durbin (Author/Creator) - Bloomberg (United States)S.A. Diehl (Author/Creator) - University of VermontC. Cerpas (Author/Creator) - Ministry of HealthA. Balmaseda (Author/Creator) - Ministry of HealthG. Kuan (Author/Creator) - Ministry of HealthJ. Coloma (Author/Creator) - University of California, BerkeleyE. Harris (Author/Creator) - University of California, BerkeleyJ.E. Crowe (Author/Creator) - Vanderbilt University Medical CenterM. Stone (Author/Creator) - Blood Systems Research InstituteP.J. Norris (Author/Creator) - Blood Systems Research InstituteM. Busch (Author/Creator) - Blood Systems Research InstituteH. Vivanco-Cid (Author/Creator) - Universidad VeracruzanaJ. Cox (Author/Creator) - Vaccine Research CenterB.S. Graham (Author/Creator) - Vaccine Research CenterJ.E. Ledgerwood (Author/Creator) - Vaccine Research CenterL. Turtle (Author/Creator) - Health Protection Research Unit in Emerging and Zoonotic Infections at University of LiverpoolT. Solomon (Author/Creator) - Health Protection Research Unit in Emerging and Zoonotic Infections at University of LiverpoolE.G. Kallas (Author/Creator) - Universidade de São PauloD.I. Watkins (Author/Creator) - University of MiamiD. Weiskopf (Author/Creator) - La Jolla Institute for ImmunologyA. Sette (Author/Creator) - La Jolla Institute for ImmunologyT.S. Dermody (Author/Creator)
- Publication Details
- Journal of Virology, Vol.91(24)
- Publisher
- American Society for Microbiology
- Identifiers
- 991005543309207891
- Copyright
- © 2017 American Society for Microbiology
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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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