Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/22837
Title: Prior Dengue virus exposure shapes T cell immunity to Zika virus in humans
Authors: Pinto, Luzia Maria de Oliveira
Azeredo, Elzinandes Leal de
Affilliation: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ. Brasil.
Múltipla - ver em Notas
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.IMPORTANCE The issue of potential ZIKV and DENV cross-reactivity and how pre-existing DENV T cell immunity modulates ZIKA T cell responses is of great relevance as the two viruses often co-circulate and ZIKA virus has been spreading in geographical regions where DENV is endemic or hyper-endemic. Our data show that memory T cell responses elicited by prior infection with DENV recognize ZIKV-derived peptides and that DENV exposure prior to ZIKV infection influences the timing, magnitude and quality of the T cell response. Additionally we show that ZIKV-specific responses target different proteins than DENV-specific responses, pointing towards important implications for vaccine design against this global threat.
Keywords: Heterologus immunity
Cross-reactivity
Immunodominance
ZIKV
Dengue virus (DENV)
Zika virus
Flavirus
T Cells
keywords: Dengue
Vírus Zika
Issue Date: 2017
Publisher: American Society for Microbiology
Citation: GRIFONI, Alba et al. Prior Dengue virus exposure shapes T cell immunity to Zika virus in humans. J. Virol. p. 1-56, Oct. 2017.
Description: Autors: Grifoni A1, Pham J1, Sidney J1, O'Rourke PH1, Paul S1, Peters B1, Martini SR1, de Silva AD1,2, Ricciardi MJ3, Magnani DM3, Silveira CGT4, Maestri A4, Costa PR4, de-Oliveira-Pinto LM5, de Azeredo EL5, Damasco PV6, Phillips E7, Mallal S7, de Silva AM8, Collins M8, Durbin A9, Diehl SA10, Cerpas C11, Balmaseda A11, Kuan G12, Coloma J13, Harris E13, Crowe JE Jr14, Stone M15, Norris PJ15, Busch M15, Vivanco-Cid H16, Cox J17, Graham BS17, Ledgerwood JE17, Turtle L18,19,20, Solomon T19,21,22, Kallas EG4, Watkins DI3, Weiskopf D1, Sette A23. AUTOR INFORMATION:- 1 Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA. 2- Genetech Research Institute, Colombo, Sri Lanka. 3 - Department of Pathology, University of Miami Miller School of Medicine, Miami, FL. 4 - Division of Clinical Immunology and Allergy, School of Medicine, University of São Paulo, Brazil. 5 - Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. 6 - Federal University of the State of Rio de Janeiro (UNIRIO). 7 - Institute for Immunology and Infectious Diseases, Murdoch University, Perth, Western Australia, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN. 8 - Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC. 9 - Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD. 10 - University of Vermont, School of Medicine, Burlington, VT. 11 - National Virology Laboratory, National Center for Diagnosis and Reference, Ministry of Health, Managua, Nicaragua. 12 - Health Center Sócrates Flores Vivas, Ministry of Health, Managua, Nicaragua. 13 - Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, USA. 14 - Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN. 15 - Blood Systems Research Institute, San Francisco, CA. 16 - Instituto de Investigaciones Medico-Biologicas, Universidad Veracruzana, Veracruz, Mexico. 17 - Vaccine Research Center, NIAID, NIH, Bethesda, MD. 18 - Centre for Global Vaccine Research, Institute of Infection and Global Health, University of Liverpool, 8 West Derby Street, Liverpool, L69 7BE, UK. 19 - NIHR Health Protection Research Unit for Emerging and Zoonotic Infections, University of Liverpool, 8 West Derby Street, Liverpool, L69 7BE, UK. 20 - Tropical & Infectious Disease Unit, Royal Liverpool University Hospital, Liverpool, L7 8XP, UK. 21 - Institute of Infection and Global Health, University of Liverpool, 8 West Derby Street, Liverpool, L69 7BE, UK. 22 - Walton Centre NHS Foundation Trust, Liverpool, L9 7LJ, UK. 23 - Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA alex@lji.org.
DOI: 10.1128/JVI.01469-17
Copyright: open access
Revised document: Não
Publication status: Não publicado
Appears in Collections:IOC - Preprint

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