Abstract
Bovine coronavirus (BCoV) infection that causes disease outbreaks among farm animals, resulting in significant economic losses particularly in the cattle industry, has the potential to become zoonotic. miRNAs, which are short non-coding segments of RNA that inhibits the expression of their target genes, have been identified as potential biomarkers and drug targets, though this potential in BCoV remains largely unknown. We hypothesize that certain miRNAs could simultaneously target multiple genes, are significantly conserved across many species, thereby demonstrating the potential to serve as diagnostic or therapeutic tools for bovine coronavirus infection. To this end, we utilized different existing and publicly available computational tools to conduct system analysis predicting important miRNAs that could affect BCoV pathogenesis. Eleven genes including CEBPD, IRF1, TLR9, SRC, and RHOA, significantly indicated in immune-related pathways, were identified to be associated with BCoV, and implicated in other coronaviruses. Of the 70 miRNAs predicted to target the identified genes, four concomitant miRNAs (bta-miR-11975, bta-miR-11976, bta-miR-22-3p, and bta-miR-2325c) were found. Examining the gene interaction network suggests IL-6, IRF1, and TP53 as key drivers. Phylogenetic analysis revealed that miR-22 was completely conserved across all 14 species it was searched against, suggesting a shared and important functional role. Functional annotation and associated pathways of target genes, such as positive regulation of cytokine production, IL-6 signaling pathway, and regulation of leukocyte differentiation, indicate the miRNAs are major participants in multiple aspects of both innate and adaptive immune response. Examination of variants evinced a potentially deleterious SNP in bta-miR-22-3p and an advantageous SNP in bta-miR-2325c. Conclusively, this study provides new insight into miRNAs regulating genes responding to BCoV infection, with bta-miR-22-3p particularly indicated as a potential drug target or diagnostic marker for bovine coronavirus.
Highlights
Coronaviruses are pathogenic RNA viruses of the subfamily Coronovirinae, engendering severe disease in many bird and mammalian species, such diseases becoming fatal in chickens, pigs, cattle, dogs, and mice (Fehr and Perlman, 2015; Amer, 2018; Ellis, 2019)
This study aims to elucidate the role of miRNAs in the host immune response to Bovine coronavirus (BCoV), demonstrate miRNA-target interactions, identify potential markers for disease diagnosis, and possible therapeutic drug targets
Since literature pertaining to gene expression in BCoV is limited, further stipulations were placed on the 77 seed genes to ascertain if the gene was significant in the disease
Summary
Coronaviruses are pathogenic RNA viruses of the subfamily Coronovirinae, engendering severe disease in many bird and mammalian species, such diseases becoming fatal in chickens, pigs, cattle, dogs, and mice (Fehr and Perlman, 2015; Amer, 2018; Ellis, 2019) They are responsible for the ongoing COVID19 pandemic and the attendant significant morbidity and mortality (Gussow et al, 2020; Lucas et al, 2020). BCoV has high mortality rates in calves, inducing wasting and flattening of the villi in the GI and a substantial cause of calf diarrhea It is indicated in winter dysentery, and drives the consequent decrease in milk production in adult cattle. Due to the paucity of information on bovine coronaviruses, the possible consequences arising from the current pandemic and its potential to become zoonotic, more research is needed to understand and disentangle hostvirus interaction in the context of immune response and disease pathogenesis
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