The orf virus 129 protein can inhibit immune responses by interacting with host complement C1q binding protein in goat turbinate bone cells.

Yixin Dan, Lu Yang, Huanrong Zhang, Yupeng Ren, Honghong He, Falong Yang, Jiangjiang Zhu, Hua Xiang

Veterinary microbiology 2023 Aug

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Contagious ecthyma is a severe and highly contagious disease caused by an orf virus (ORFV). The virus is responsible for substantial economic losses in the goat industry and threatens humans. We previously determined the role of ORFV129 protein, one of the five ankyrin-repeat proteins coded by the orf genome, in suppressing the transcription of pro-inflammatory cytokines IL-6, IL-1β and IFN-γ. In the present study, we identified 14 cellular proteins (complement C1q binding protein [C1QBP], MCM7, EIF5A, PKM, SLC6A, TSPAN6, ATP6AP2, GPS1, MMADHC, HSPB6, SLC35B1, MTF1, P3H4, and IL15RA) that interact with ORFV129 using a yeast two-hybrid system in goat turbinate bone cells (GFTCs). The interaction between ORFV129 and (C1QBP), an immune-related protein, was confirmed using immunofluorescence co-localization and co-immunoprecipitation assays. C1QBP overexpression inhibited ORFV replication, whereas the knockdown of C1QBP promoted ORFV replication in GFTCs. Furthermore, ORFV or ORFV129 increased C1QBP expression in GFTCs, indicated that ORFV129-C1QBP interaction might contribute to the ORFV-induced host immune process. In addition, our research showed that ORFV increased the expression of ORFV129, cytokine IL-6, IL-1β and IFN-γ. C1QBP overexpression induced IFN-γ production and reduced IL-6 and IL-1β production. Conversely, C1QBP knockdown induced IL-1β production and reduced IFN-γ and IL-1β production. Moreover, augmentation of ORFV129 expression enhanced the inhibition of the secretion of cytokines IL-6, IL-1β, and IFN-γ induced by the altered expression of C1QBP. These findings suggest different downstream pathways might be involved in regulating different cytokines induced by ORFV129 expression in GFTCs. Copyright © 2023 Elsevier B.V. All rights reserved.

Citation

Yixin Dan, Lu Yang, Huanrong Zhang, Yupeng Ren, Honghong He, Falong Yang, Jiangjiang Zhu, Hua Xiang. The orf virus 129 protein can inhibit immune responses by interacting with host complement C1q binding protein in goat turbinate bone cells. Veterinary microbiology. 2023 Aug;283:109782