Analysis of tRNA halves (tsRNAs) in serum from cattle challenged with bovine viral diarrhea virus

Authors: Taxis, Tasia; BAUERMANN, FERNANDO - South Dakota State University; Ridpath, Julia; Casas, Eduardo

Submitted to: Genetics and Molecular Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/4/2018
Publication Date: 6/27/2019
Citation: Taxis, T.M., Bauermann, F.V., Ridpath, J.F., Casas, E. 2019. Analysis of tRNA halves (tsRNAs) in serum from cattle challenged with bovine viral diarrhea virus. Genetics and Molecular Biology. 42(2). https://dx.doi.org/10.1590/1678-4685-GMB-2018-0019.
DOI: https://doi.org/10.1590/1678-4685-GMB-2018-0019

Interpretive Summary: Pieces of tRNA molecules, called tRFs, can be found in the blood of cattle and have recently been associated with gene expression/regulation and disease in mammals. We have identified tRFs that differed in abundance, or amount, between control animals and animals that had a viral infection caused by bovine viral diarrhea virus (BVDV). Cattle infected with this virus have a lower immune system and may also develop secondary infections, such as respiratory disease. This leads to financial loss for the producer. By identifying tRFs associated with BVDV infections in cattle, the scientific community will continue to learn of the role tRFs play in an immune response to a viral infection. Potentially, results from this study provide the first step in identifying possible markers for producers or veterinarians to use in order to identify a BVDV infection in a herd of cattle.

Technical Abstract: Bovine viral diarrhea viruses (BVDV) consists of two species within the Pestivirus genus that can lead to significant economic loss in cattle. Acute infections of BVDV lead to a wide range of clinical presentations ranging from subclinical to severe, depending on viral strain, immune and reproductive status of the animal, stress and the presence of secondary pathogens. Given this variation, BVDV infection cannot be diagnosed based on definitive clinical presentations. Diagnosis based on detection by laboratory tests depend on collection of samples during a relatively short viremia which does not correspond to the peak observation of clinical presentation. For these reasons, acutely infected animals remain largely undiagnosed, leading to an underestimation of the impact of BVDV infections. Further, the immunosuppression associated with BVDV infections may persist after the virus has been cleared. Small non-coding transfer RNA fragments (tRFs) are hypothesized to function and possibly compete with microRNAs, to regulate gene expression during an immune response. The objective of this study was to identify circulating tRFs in cattle that had been challenged with a non-cytopathic field strain of BVDV. Colostrum-deprived neonatal Holstein calves were either challenged with BVDV (n=5) or mock challenged with Madin Darby bovine kidney lysate (n=4). Sera was collected prior to challenge and days 4, 9, and 16 post challenge. RNA was extracted and expression of small non-coding RNAs were obtained using next-generation sequencing. A total of 87,838,207 reads identified 41 different tRFs, of which 18 had > 5,000 total reads. Two tRF5s, tRF5ProAGG (P=0.03) and tRF5ValAAC (P=0.03), differed across time. Two tRF5s, tRF5GlyCCC (P=0.03) and tRF5GlyGCC (P=0.04), differed between treatment groups across time. Four days post challenge, tRF5GlyCCC (P=0.01) and tRF5GlyGCC (P=0.01) were significantly lower in the challenged group than the control group. While no other significant differences were found between treatment groups at other times, both tRF5s tended to have a lower count number in the challenged group until 9 days post challenge. Further studies are needed to identify the importance and function of tRF5GlyCCC and tRF5GlyGCC in serum samples of cattle challenged with BVDV.