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Title: Proof-of-concept study: profile of circulating micro RNAs in bovine serum harvested during acute and persistent FMDV infection

Author
item STENFELDT, CAROLINA - Oak Ridge Institute For Science And Education (ORISE)
item Arzt, Jonathan
item SMOLIGA, GEORGE - Oak Ridge Institute For Science And Education (ORISE)
item Larocco, Michael
item GUTKOSKA, JOSEPH - Oak Ridge Institute For Science And Education (ORISE)
item Lawrence, Paul

Submitted to: Virology Journal
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/29/2017
Publication Date: 4/7/2017
Citation: Stenfeldt, C., Arzt, J., Smoliga, G., Larocco, M.A., Gutkoska, J., Lawrence, P.J. 2017. Proof-of-concept study: profile of circulating micro RNAs in bovine serum harvested during acute and persistent FMDV infection. Virology Journal. 14:71. doi: 10.1186/s12985-017-0743-3.

Interpretive Summary: MicroRNAs are recently discovered small RNAs present in humans and animals that can increase and decrease in response to disease. These small RNA have been used as signatures to detect diseases in animals including cancer, bacterial infections, and viral infections. Here, we searched for microRNAs that are associated with foot-and-mouth disease virus (FMDV) infection in cattle. Foot-and-mouth disease is a devastating disease that is economically disastrous. We hope that the identification of microRNAs unique to FMDV will help us with the development of new rapid diagnostics, therapeutic treatments, and novel vaccines. Here, 19 microRNAs were observed to be either elevated or decreased in response to FMDV in the blood of cattle at different phases of FMDV infection. We now know what microRNAs are associated with different stages of FMDV infection. Indeed, we also found seven microRNAs that were unique to persistent FMDV infection, a disease state with which we know little about. These findings will contribute to the global efforts to contain and eradicate FMDV.

Technical Abstract: Expression of 144 distinct bovine microRNAs (miRNAs) was quantified in bovine serum harvested during different phases of infection with foot-and-mouth disease virus (FMDV). There were marked differences in miRNA expression between acute, persistent, and convalescent phases of infection. During acute infection, 7 miRNAs were significantly up-regulation while 3 targets were down-regulated. The highest up- regulation was measured for miR-17-5p while miR-1281 was most significantly down-regulated. During persistent infection, 9 miRNAs were up-regulated with the highest fold-change measured for miR-31. Persistent infection was also associated with significant down-regulation of miR-1281. In contrast to this, miRNA expression in cattle that had cleared infection was more similar to baseline levels, with only two significantly regulated targets (decreased miR-455-3p and increased miR-150). miRNAs identified as significantly regulated during FMDV infection were associated with cellular proliferation, apoptosis, or modulation of the host immune response. The findings from this study suggest an important role of non-coding regulatory RNAs in the FMDV life cycle in cattle. Future studies will delineate the individual contributions of the reported miRNAs to FMDV replication and may facilitate development of novel diagnostic applications.