Equine arteritis virus (EAV) can establish long-term persistent infection in the reproductive tract of stallions and is shed in the semen. Previous studies showed that long-term persistence is associated with a specific allele of the CXCL16 gene (CXCL16S) and that persistent infection is maintained despite the presence of a local inflammatory and humoral and mucosal antibody responses. In this study, we demonstrated that equine seminal exosomes (SEs) are enriched in a small subset of microRNAs (miRNAs). Most importantly, we demonstrated that long-term EAV persistence is associated with the downregulation of an SE-associated miRNA (eca-mir-128) and with an enhanced expression of CXCL16 in the reproductive tract, a putative target of eca-mir-128. The findings presented here suggest that SE eca-mir-128 is implicated in the regulation of the CXCL16/CXCR6 axis in the reproductive tract of persistently infected stallions, a chemokine axis strongly implicated in EAV persistence. This is a novel finding and warrants further investigation to identify its specific mechanism in modulating the CXCL16/CXCR6 axis in the reproductive tract of the EAV long-term carrier stallion.
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This study was supported by Agriculture and Food Research Initiative competitive grant number 2013-68004-20360 from the USDA National Institute of Food and Agriculture. This work was also supported by USDA National Institute of Food and Agriculture hatch project number KY014055 (College of Agriculture, Food and Environment, University of Kentucky).
Supplemental material for this article may be found at https://doi.org/10.1128/JVI.00015-18.
The RNA sequencing data from this study were deposited in the Gene Expression Omnibus (GEO, NCBI, NIH) database under study GSE108180 (accession numbers GSM2891902 to GSM2891909).
Carossino, Mariano; Dini, Pouya; Kalbfleisch, Theodore S.; Loynachan, Alan T.; Canisso, Igor F.; Shuck, Kathleen M.; Timoney, Peter J.; Cook, R. Frank; and Balasuriya, Udeni B. R., "Downregulation of MicroRNA Eca-Mir-128 in Seminal Exosomes and Enhanced Expression of CXCL16 in the Stallion Reproductive Tract Are Associated with Long-Term Persistence of Equine Arteritis Virus" (2018). Maxwell H. Gluck Equine Research Center Faculty Publications. 19.