Human T cell responses to Dengue and Zika virus infection compared to Dengue/Zika coinfection

Introduction: Zika virus (ZIKV) and dengue virus (DENV) co-circulated during latest outbreaks in Brazil, hence, it is important to evaluate the host cross-reactive immune responses to these viruses. So far, little is known about human T cell responses to ZIKV and no reports detail adaptive immune responses during DENV/ZIKV coinfection. Methods: Here, we studied T cells responses in well-characterized groups of DENV, ZIKV, or DENV/ZIKV infected patients and DENV-exposed healthy donors. We evaluated chemokine receptors expression and single/multifunctional frequencies of IFN gamma, TNF, and IL2-producing T cells during these infections. Even without antigenic stimulation, it was possible to detect chemokine receptors and IFN gamma, TNF, and IL2-producing T cells from all individuals by flow cytometry. Additionally, PBMCs' IFN gamma response to DENV NS1 protein and to polyclonal stimuli was evaluated by ELISPOT. Results: DENV and ZIKV infections and DENV/ZIKV coinfections similarly induced expression of CCR5, CX3CR1, and CXCR3 on CD4 and CD8 T cells. DENV/ZIKV coinfection decreased the ability of CD4(+) T cells to produce IFN gamma(+), TNF+, TNF+IFN gamma(+), and TNF(+)IL2(+), compared to DENV and ZIKV infections. A higher magnitude of IFN response to DENV NS1 was found in donors with a history of dengue infection, however, a hyporesponsiveness was found in acute DENV, ZIKV, or DENV/ZIKV infected patients, even previously infected with DENV. Conclusion: Therefore, we emphasize the potential impact of coinfection on the immune response from human hosts, mainly in areas where DENV and ZIKV cocirculate.