Impact of Zika Virus on the Human Type I Interferon Osteoimmune Response

ABSTRACT: 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. Both ZIKV and IFN suppress proteins associated with microcephaly/pseudo-TORCH syndrome (BI1, KIF20 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.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Osteoblast

DISEASE(S): Zika Virus Congenital Syndrome

SUBMITTER: Matthew Berberich  

LAB HEAD: Dahlene N. Fusco MD PhD

PROVIDER: PXD016398 | Pride | 2020-11-03

REPOSITORIES: Pride