TY - JOUR
T1 - Prior dengue virus exposure shapes T cell immunity to Zika virus in humans
AU - Grifoni, Alba
AU - Pham, John
AU - Sidney, John
AU - O'Rourke, Patrick H.
AU - Paul, Sinu
AU - Peters, Bjoern
AU - Martini, Sheridan R.
AU - de Silva, Aruna D.
AU - Ricciardi, Michael J.
AU - Magnani, Diogo M.
AU - Silveira, Cassia G.T.
AU - Maestri, Alvino
AU - Costa, Priscilla R.
AU - de-Oliveira-Pinto, Luzia Maria
AU - de Azeredo, Elzinandes Leal
AU - Damasco, Paulo Vieira
AU - Phillips, Elizabeth
AU - Mallal, Simon
AU - de Silva, Aravinda M.
AU - Collins, Matthew
AU - Durbin, Anna
AU - Diehl, Sean A.
AU - Cerpas, Cristhiam
AU - Balmaseda, Angel
AU - Kuan, Guillermina
AU - Coloma, Josefina
AU - Harris, Eva
AU - Crowe, James E.
AU - Stone, Mars
AU - Norris, Phillip J.
AU - Busch, Michael
AU - Vivanco-Cid, Hector
AU - Cox, Josephine
AU - Graham, Barney S.
AU - Ledgerwood, Julie E.
AU - Turtle, Lance
AU - Solomon, Tom
AU - Kallas, Esper G.
AU - Watkins, David I.
AU - Weiskopf, Daniela
AU - Sette, Alessandro
N1 - Funding Information:
This work was supported by National Institutes of Health contracts and grants HHSN272200900042C, HHSN27220140045C, and U19 AI118626-01 to A.S., HHSN268201100001I to BSRI, 1P01AI106695-01A1 to E.H., and RO1 AI127828 to J.E.C. Further support was provided by ZikaPLAN, which has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement no. 734584, to A.S., by BMGF grant 457 OPP1104710 to A.P.D., an internal grant from the University of Miami Clinical and Translational Research Institute to D.I.W., and grants from Consejo Nacional de Ciencia y Tecnología (CONACyT) Fonteras de la
Publisher Copyright:
© 2017 American Society for Microbiology.
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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 preexisting 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-preexposed 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 from DENV-preexposed donors selectively upregulated granzyme B and PD1, unlike DENV-naive 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.
AB - 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 preexisting 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-preexposed 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 from DENV-preexposed donors selectively upregulated granzyme B and PD1, unlike DENV-naive 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.
KW - Cross-reactivity
KW - DENV
KW - Heterologous immunity
KW - Immunodominance
KW - T cells
KW - ZIKV
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UR - http://www.scopus.com/inward/citedby.url?scp=85035768097&partnerID=8YFLogxK
U2 - 10.1128/JVI.01469-17
DO - 10.1128/JVI.01469-17
M3 - Article
C2 - 28978707
AN - SCOPUS:85035768097
VL - 91
JO - Journal of Virology
JF - Journal of Virology
SN - 0022-538X
IS - 24
M1 - e01469-17
ER -