Abstract
Despite decades of extensive research, bovine respiratory disease (BRD) remains the most devastating disease in beef cattle production. Establishing a clinical diagnosis often relies upon visual detection of non-specific signs, leading to low diagnostic accuracy. Thus, post-weaned beef cattle are often metaphylactically administered antimicrobials at facility arrival, which poses concerns regarding antimicrobial stewardship and resistance. Additionally, there is a lack of high-quality research that addresses the gene-by-environment interactions that underlie why some cattle that develop BRD die while others survive. Therefore, it is necessary to decipher the underlying host genomic factors associated with BRD mortality versus survival to help determine BRD risk and severity. Using transcriptomic analysis of at-arrival whole blood samples from cattle that died of BRD, as compared to those that developed signs of BRD but lived (n = 3 DEAD, n = 3 ALIVE), we identified differentially expressed genes (DEGs) and associated pathways in cattle that died of BRD. Additionally, we evaluated unmapped reads, which are often overlooked within transcriptomic experiments. 69 DEGs (FDR<0.10) were identified between ALIVE and DEAD cohorts. Several DEGs possess immunological and proinflammatory function and associations with TLR4 and IL6. Biological processes, pathways, and disease phenotype associations related to type-I interferon production and antiviral defense were enriched in DEAD cattle at arrival. Unmapped reads aligned primarily to various ungulate assemblies, but failed to align to viral assemblies. This study further revealed increased proinflammatory immunological mechanisms in cattle that develop BRD. DEGs upregulated in DEAD cattle were predominantly involved in innate immune pathways typically associated with antiviral defense, although no viral genes were identified within unmapped reads. Our findings provide genomic targets for further analysis in cattle at highest risk of BRD, suggesting that mechanisms related to type I interferons and antiviral defense may be indicative of viral respiratory disease at arrival and contribute to eventual BRD mortality.
Highlights
Extensively researched, bovine respiratory disease (BRD) continues to be the most significant disease in post-weaned beef cattle in North America
Biological processes, pathways, and disease phenotype associations related to type-I interferon production and antiviral defense were enriched in DEAD cattle at arrival
Multidimensional scaling (MDS; Fig 1), which depicts the similarity of expression profiles between each animal in the analysis, demonstrated clustering of the three DEAD cattle
Summary
Bovine respiratory disease (BRD) continues to be the most significant disease in post-weaned beef cattle in North America. BRD is a multifactorial disease complex, with contributing causative factors including primary viral infection, bacterial colonization of the upper and lower respiratory tract, and stressful events related to abrupt weaning, co-mingling with recently transported cattle, and novel feeding or housing environments [1,2,3,4,5] These factors result in host-pathogen interactions that are exceedingly complex and definitive diagnosis of the inciting etiological agent(s) is not usually made. BRD diagnosis will typically rely on non-specific clinical signs including elevated rectal temperature, depressed demeanor, increased respiratory rate and effort, and anorexia [5,6,7,8]. We evaluated unmapped reads, which are often overlooked within transcriptomic experiments
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