Drouin Arnaud, Wallbillich Nicholas, Theberge Marc, Liu Sharon, Katz Joshua, Bellovoda Kamela, Se Yun Cheon Scarlett, Gootkind Frederick, Bierman Emily, Zavras Jason, Berberich Matthew J, Kalocsay Marian, Guastaldi Fernando, Salvadori Nicolas, Troulis Maria, Fusco Dahlene N
Department of Medicine, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA, 70114, United States; Department of Pathology, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA, 70114, United States.
Department of Medicine, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA, 70114, United States.
Cytokine. 2021 Jan;137:155342. doi: 10.1016/j.cyto.2020.155342. Epub 2020 Oct 30.
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.
Osteoblast-like Saos-2 cells are permissive to ZIKV and responsive to IFN.
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.
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.
Transient ZIKV infection influences osteoimmune state, and IFN and ZIKV activate distinct proteomes in Saos-2 cells, which could inform therapeutic, engineered, disruptions.
骨免疫学这一新兴领域支持成骨细胞中干扰素（IFN）反应途径的重要性。阐明成骨细胞与IFN的相互作用很重要，因为IFN被用作挽救性抗肿瘤治疗，但全身毒性高且临床结果各异。此外，成骨细胞对病毒感染诱导的IFN途径的全身性爆发和破坏的反应可能会影响骨重塑。寨卡病毒（ZIKV）感染会影响人类的骨骼发育和体外IFN反应。一致地，已有报道称人类成骨细胞对ZIKV具有易感性的初步证据。
成骨样Saos-2细胞对ZIKV易感且对IFN有反应。
采用多种方法评估Saos-2细胞是否对ZIKV感染易感并表现出IFN介导的ZIKV抑制作用。使用蛋白质组学方法评估ZIKV和IFN对Saos-2细胞的影响。
有证据证实Saos-2细胞对ZIKV易感并支持IFN介导的ZIKV抑制。ZIKV和IFN对Saos-2蛋白质组有不同影响，以HELZ2蛋白为例，该蛋白由IFN上调但对ZIKV无反应。ZIKV和IFN均抑制与小头畸形/假TORCH综合征相关的蛋白质（BI1、KI20A和UBP18），且ZIKV诱导潜在的进入因子PLVAP。
短暂的ZIKV感染会影响骨免疫状态，且IFN和ZIKV在Saos-2细胞中激活不同的蛋白质组，这可为治疗、工程干预提供参考。
