Refining our understanding of how calves respond to viral infections

Background

Bovine respiratory disease (BRD) is diagnosed based on clinical signs, but the specific pathogen involved is not typically identified. Bovine coronavirus (BCoV) is widely prevalent in nasal secretions at feedlot arrival in both healthy and sick calves. An earlier BCRC-funded study (ANH.20.20) found BCoV much more frequently in calves that were treated for BRD than in healthy pen mates sampled at the same time.

Understanding gene expression in response to BRD infection is critical to improve both disease diagnostics and disease control in cattle. It is difficult to study how cattle regulate the expression of their immunity genes in response to a natural infection because it’s impossible to know exactly what they were exposed to, when they were exposed, and what the pathogen dose was. Experimental challenge trials control all these factors and generate information that can help evaluate vaccination strategies and compare vaccine responses related to the specific immune responses. It can also characterize how the immune response evolves at different stages of BCoV infection, ultimately leading to more reproducible and clear challenge models.

The nose is the best place to study the host’s immune response to respiratory infections, because that’s where respiratory pathogens encounter the animal, but there have been very few studies of how immunity genes are expressed in either natural infections or challenge models. Nasal swabs may be a useful way to collect samples needed to study early changes in host gene expression and may indicate whether the animal is responding to a harmful (pathogenic) or harmless (commensal) form of BCoV.

This study will investigate differences in the immune response of calves challenged with BCoV or not. They will characterize and compare differences in gene expression (the “transcriptome”) in both the nose and blood.

objectives

• Investigate differences in the immune response of calves challenged with BCoV compared to unchallenged calves by characterizing and comparing the transcriptome at both the local nasal interface and systemically in whole blood

what they will do

Ten 7-week-old calves will be used for this study. Whole blood (systemic immune response), nasal swab (mucosal immune response) and fecal samples will be collected from all calves, then half will be challenged with BCoV (the other five will not). Calves will be monitored by a veterinarian every second day to score clinical signs. Samples will be collected again when symptoms appear and when the calves are euthanized on day 12. Viral loads, host immune gene expression and anti-BCoV antibody levels will be evaluated from these samples. Lung damage will be evaluated after the calves are euthanized.

implications

This study will identify biomarkers for different stages of BCoV infection and disease progression. It will also test the potential value of immune gene expression in disease challenge models and vaccination programs for other viruses involved in BRD. A better understanding of how cattle respond to viruses (in general and to specific viral infections) will help us evaluate vaccine effectiveness more effectively.