BACKGROUND The developing field of osteoimmunology supports importance of an interferon (IFN) response pathway in osteoblasts. Clarifying osteoblast-IFN interactions is important because IFN is used as salvage anti-tumor therapy but systemic toxicity is high with variable clinical results. In addition, osteoblast response to systemic bursts and disruptions of IFN pathways induced by viral infection may influence bone remodeling. ZIKA virus (ZIKV) infection impacts bone development in humans and IFN response in vitro. Consistently, initial evidence of permissivity to ZIKV has been reported in human osteoblasts. HYPOTHESIS Osteoblast-like Saos-2 cells are permissive to ZIKV and responsive to IFN. METHODS Multiple approaches were used to assess whether Saos-2 cells are permissive to ZIKV infection and exhibit IFN-mediated ZIKV suppression. Proteomic methods were used to evaluate impact of ZIKV and IFN on Saos-2 cells. RESULTS Evidence is presented confirming Saos-2 cells are permissive to ZIKV and support IFN-mediated suppression of ZIKV. ZIKV and IFN differentially impact the Saos-2 proteome, exemplified by HELZ2 protein which is upregulated by IFN but non responsive to ZIKV. Both ZIKV and IFN suppress proteins associated with microcephaly/pseudo-TORCH syndrome (BI1, KI20A and UBP18), and ZIKV induces potential entry factor PLVAP. CONCLUSIONS Transient ZIKV infection influences osteoimmune state, and IFN and ZIKV activate distinct proteomes in Saos-2 cells, which could inform therapeutic, engineered, disruptions.

中文翻译：

---

寨卡病毒对人类 I 型干扰素骨免疫反应的影响


背景技术骨免疫学的发展领域支持干扰素(IFN)反应途径在成骨细胞中的重要性。阐明成骨细胞与 IFN 的相互作用非常重要，因为 IFN 被用作挽救性抗肿瘤治疗，但全身毒性很高，临床结果各异。此外，成骨细胞对病毒感染引起的全身爆发和干扰素途径破坏的反应可能会影响骨重塑。寨卡病毒 (ZIKV) 感染会影响人类骨骼发育和体外干扰素反应。一致地，在人类成骨细胞中已经报道了 ZIKV 的易感性的初步证据。假设 成骨细胞样 Saos-2 细胞对 ZIKV 敏感，并对 IFN 敏感。方法 采用多种方法评估 Saos-2 细胞是否允许 ZIKV 感染并表现出 IFN 介导的 ZIKV 抑制。使用蛋白质组学方法评估 ZIKV 和 IFN 对 Saos-2 细胞的影响。结果 证据证实 Saos-2 细胞对 ZIKV 具有耐受性，并支持 IFN 介导的 ZIKV 抑制。 ZIKV 和 IFN 对 Saos-2 蛋白质组的影响存在差异，以 HELZ2 蛋白为例，IFN 上调该蛋白，但对 ZIKV 无反应。 ZIKV 和 IFN 均抑制与小头畸形/假性 TORCH 综合征相关的蛋白（BI1、KI20A 和 UBP18），并且 ZIKV 诱导潜在的进入因子 PLVAP。结论 短暂的 ZIKV 感染影响骨免疫状态，IFN 和 ZIKV 激活 Saos-2 细胞中不同的蛋白质组，这可以为治疗、工程设计和破坏提供信息。