Laboratory of Viral Immunology, Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Rio de Janeiro, Brazil.
Laboratory of Genetics, Institute of Paediatrics and Puericulture Martagão Gesteira (IPPMG), Federal University of Rio de Janeiro, UFRJ, Rio de Janeiro, Brazil.
Immun Inflamm Dis. 2018 Jun;6(2):194-206. doi: 10.1002/iid3.203. Epub 2017 Dec 28.
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.
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.
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.
Therefore, we emphasize the potential impact of coinfection on the immune response from human hosts, mainly in areas where DENV and ZIKV cocirculate.
寨卡病毒（ZIKV）和登革热病毒（DENV）在巴西最近的疫情中共同传播，因此，评估宿主对这些病毒的交叉反应性免疫反应非常重要。到目前为止，人们对人类对 ZIKV 的 T 细胞反应知之甚少，也没有报道详细描述 DENV/ZIKV 合并感染期间的适应性免疫反应。
在这里，我们研究了在经过充分特征描述的 DENV、ZIKV 或 DENV/ZIKV 感染患者以及 DENV 暴露的健康供体组中的 T 细胞反应。我们评估了趋化因子受体表达和 IFNγ、TNF 和 IL2 产生 T 细胞的单/多功能频率，在这些感染期间。即使没有抗原刺激，通过流式细胞术也可以从所有个体中检测到趋化因子受体和 IFNγ、TNF 和 IL2 产生的 T 细胞。此外，通过 ELISPOT 评估了 PBMCs 对 DENV NS1 蛋白和多克隆刺激物的 IFNγ 反应。
DENV 和 ZIKV 感染以及 DENV/ZIKV 合并感染同样诱导了 CD4 和 CD8 T 细胞上 CCR5、CX3CR1 和 CXCR3 的表达。与 DENV 和 ZIKV 感染相比，DENV/ZIKV 合并感染降低了 CD4 T 细胞产生 IFNγ、TNF、TNF IFNγ 和 TNF IL2 的能力。在有登革热感染史的供体中发现对 DENV NS1 的 IFNγ 反应幅度更高，但在急性 DENV、ZIKV 或 DENV/ZIKV 感染患者中发现反应降低，即使以前感染过 DENV。
因此，我们强调了合并感染对人类宿主免疫反应的潜在影响，特别是在 DENV 和 ZIKV 共同传播的地区。
