Abstract：
During the course of acute ZIKV infection, pruritus is a cardinal symptom widely documented in the literature. Its frequent association with dysesthesia and several dysautonomic manifestations, suggests a pathophysiological mechanism involving the peripheral nervous system. The aim of this study was to develop a functional human model to potentially able to be infected by ZIKV: by demonstrating the functionality on a new human model of co-culture of keratinocyte and sensory neuron derived from induced pluripotent stem cells using a classical method of capsaicin induction and SP release, and verify the presence of ZIKV entry receptor in these cells. Depending of cellular type, receptors of the TAMs family, TIMs (TIM1, TIM3 and TIM4) and DC-SIGN and RIG1 were present/detected. The cells incubations with capsaicin resulted in an increase of the substance P. Hence, this study demonstrated the possibility to obtain co-cultures of human keratinocytes and human sensory neurons that release substance P in the same way than previously published in animal models which can be used as a model of neurogenic skin inflammation. The demonstration of the expression of ZIKV entry receptors in these cells allows to considerate the potent possibility that ZIKV is able to infect cells.
摘要：
在急性ZIKV感染过程中，瘙痒是文献中广泛记载的主要症状。它经常与感觉异常和几种自主神经失调表现有关，提示涉及周围神经系统的病理生理机制。这项研究的目的是开发一种可能被ZIKV感染的功能性人体模型：通过使用经典方法证明角质形成细胞和诱导多能干细胞衍生的感觉神经元共培养的新型人体模型的功能辣椒素诱导和SP释放，并验证这些细胞中ZIKV进入受体的存在。根据细胞类型，TAMs家族的受体，存在/检测到TIM(TIM1、TIM3和TIM4)和DC-SIGN和RIG1。与辣椒素一起孵育的细胞导致P物质的增加。因此，这项研究证明了获得人类角质形成细胞和人类感觉神经元的共培养物的可能性，其释放物质P的方式与先前在动物模型中发表的相同，该动物模型可用作神经源性皮肤炎症的模型。ZIKV进入受体在这些细胞中表达的证明允许考虑ZIKV能够感染细胞的有效可能性。
