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

Abstract

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 IFNγ, TNF, and IL2-producing T cells during these infections. Even without antigenic stimulation, it was possible to detect chemokine receptors and IFNγ, TNF, and IL2-producing T cells from all individuals by flow cytometry. Additionally, PBMCs' IFNγ 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 IFNγ⁺, TNF⁺, TNF ⁺IFNγ⁺, and TNF ⁺ IL2⁺, compared to DENV and ZIKV infections. A higher magnitude of IFNγ 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.

Since Zika virus (ZIKV) and dengue virus (DENV) co-circulated during outbreaks in Brazil, it is important to evaluate the host immune response to these viruses. Here, we studied T cells responses in well-characterized groups of DENV, ZIKV, or DENV/ZIKV infected patients and DENV-exposed healthy donors. Our main observations were: (i) most of the patients diagnosed with ZIKV were coinfected with DENV and (ii) DENV/ZIKV coinfection activate differentially CD4+ and CD8+ T cells compared to mono-infection.