Laboratory of Viral Immunology, Fundação Oswaldo Cruz, Rio de Janeiro 1040-900, Brazil.
Multiuser Laboratory for Research in Nephrology and Medical Science, School of Medicine, Universidade Federal Fluminense, Niterói, Rio de Janeiro 24 033-900, Brazil.
Viruses. 2021 Jan 28;13(2):191. doi: 10.3390/v13020191.
There have been reports of neurological abnormalities associated with the Zika virus (ZIKV), such as congenital Zika syndrome (CZS) in children born to mothers infected during pregnancy. We investigated how the immune response to ZIKV during pregnancy is primed and conduct a thorough evaluation of the inflammatory and cytotoxic profiles as well as the expression of CCR5 and CX3CR1. We compared the reactivity of T cells to ZIKV peptides in convalescent mothers infected during pregnancy. The child's clinical outcome (i.e., born with or without CZS) was taken to be the variable. The cells were stimulated in vitro with ZIKV peptides and evaluated using the ELISPOT and flow cytometry assays. After in vitro stimulation with ZIKV peptides, we observed a tendency toward a higher Interferon gamma (IFN-γ)-producing T cell responses in mothers who had asymptomatic children and a higher CD107a expression in T cells in mothers who had children with CZS. We found a higher frequency of T cells expressing CD107a+ and co-expressing CX3CR1+CCR5+, which is much clearer in the T cells of mothers who had CZS children. We suggest that this differential profile influenced the clinical outcome of babies. These data need to be further investigated, including the evaluation of other ZIKV peptides and markers and functional assays.
已有报道称寨卡病毒(ZIKV)与神经异常有关,例如感染寨卡病毒的孕妇所生婴儿的先天性寨卡综合征(CZS)。我们研究了孕妇体内针对寨卡病毒的免疫反应是如何被激活的,并对炎症和细胞毒性特征以及 CCR5 和 CX3CR1 的表达进行了全面评估。我们比较了妊娠期间感染的恢复期母亲的 T 细胞对寨卡病毒肽的反应性。将孩子的临床结局(即出生时是否患有 CZS)作为变量。将细胞在体外用寨卡病毒肽刺激,并通过 ELISPOT 和流式细胞术检测进行评估。在体外用寨卡病毒肽刺激后,我们观察到无症状儿童的母亲产生干扰素γ(IFN-γ)的 T 细胞反应有升高的趋势,而 CZS 儿童的母亲的 T 细胞中 CD107a 的表达升高。我们发现表达 CD107a+和共表达 CX3CR1+CCR5+的 T 细胞的频率更高,在患有 CZS 儿童的母亲的 T 细胞中更为明显。我们认为这种差异特征影响了婴儿的临床结局。这些数据需要进一步研究,包括对其他寨卡病毒肽和标志物以及功能测定的评估。