Differential Expression of Small Non-Coding RNAs in Serum from Cattle Challenged with Viruses Causing Bovine Respiratory Disease

MicroRNAs and tRNA-derived RNA fragments (tRFs) are the two most abundant groups of small non-coding RNAs. The potential for microRNAs and tRFs to be used as pathogen exposure indicators is yet to be fully explored. Our objective was to identify microRNAs and tRFs in cattle challenged with a non-cytopathic field strain of bovine viral diarrhea virus (BVDV) or bovine coronavirus (BoCV). Four colostrum deprived neonate calves were challenged with either BVDV (n=2) or BoCV (n=2) and 4 were mock challenged. The analysis contrasted control and challenged animals, regardless of virus type, across 3 time points: (1) pre-challenge; (2) acute response; and (3) post response. RNA was extracted from sera, and small non-coding RNAs were obtained using next-generation sequencing. The analysis included microRNAs and tRF-5s (extreme 5’ end of mature tRNA) with >1,000 total sequences and p-values ≤ 0.05. Eleven microRNAs were differentially expressed across time indicating an association with maturation or stress. Six tRF-5s were differentially expressed between control and challenged animals. Bta-miR-151-3p, was higher in control animals and differed between samples collected after acute response. One microRNA and tRF-5 were differentially expressed between control and challenged animals over time. Abundance of bta-miR-215 in challenged animals peaked at acute response while control animals remained constant. Abundance of tRF-5-GlyGCC in challenged animals remained constant across time as control animals peaked during acute response. This study has identified microRNAs associated with maturation or stress, tRF-5s associated with a challenge response, and a microRNA and tRF-5 associated with a challenge response over time.