Metagenomic characterization of the virome associated with bovine respiratory disease in feedlot cattle identified novel viruses and suggests an etiologic role for influenza D virus

Bovine respiratory disease (BRD) is the most costly disease affecting the cattle industry. The pathogenesis of BRD is complex and includes contributions from microbial pathogens as well as host, environmental and animal management factors. In this study, we utilized viral metagenomic sequencing to explore the virome of nasal swab samples obtained from feedlot cattle with acute BRD and asymptomatic pen-mates at six and four feedlots in Mexico and the USA, respectively, in April-October 2015. Twenty-one viruses were detected, with bovine rhinitis A (52.7 %) and B (23.7 %) virus, and bovine coronavirus (24.7 %) being the most commonly identified. The emerging influenza D virus (IDV) tended to be significantly associated (P=0.134; odds ratio=2.94) with disease, whereas viruses commonly associated with BRD such as bovine viral diarrhea virus, bovine herpesvirus 1, bovine respiratory syncytial virus and bovine parainfluenza 3 virus were detected less frequently. The detection of IDV was further confirmed using a real-time PCR assay. Nasal swabs from symptomatic animals had significantly more IDV RNA than those collected from healthy animals (P=0.04). In addition to known viruses, new genotypes of bovine rhinitis B virus and enterovirus E were identified and a newly proposed species of bocaparvovirus, Ungulate bocaparvovirus 6, was characterized. Ungulate tetraparvovirus 1 was also detected for the first time in North America to our knowledge. These results illustrate the complexity of the virome associated with BRD and highlight the need for further research into the contribution of other viruses to BRD pathogenesis.