Cattle have been proposed as the natural reservoir of a novel member of the virus family Orthomyxoviridae, which has been tentatively classified as influenza D virus (IDV). Although isolated from sick animals, it is unclear whether IDV causes any clinical disease in cattle. To address this aspect of Koch's postulates, three dairy calves (treatment animals) held in individual pens were inoculated intranasally with IDV strain D/bovine/Mississippi/C00046N/2014. At 1 day postinoculation, a seronegative calf (contact animal) was added to each of the treatment animal pens. The cattle in both treatment and contact groups seroconverted, and virus was detected in their respiratory tracts. Histologically, there was a significant increase in neutrophil tracking in tracheal epithelia of the treatment calves compared to control animals. While infected and contact animals demonstrated various symptoms of respiratory tract infection, they were mild, and the calves in the treatment group did not differ from the controls in terms of heart rate, respiratory rate, or rectal temperature. To mimic zoonotic transmission, two ferrets were exposed to a plastic toy fomite soaked with infected nasal discharge from the treatment calves. These ferrets did not shed the virus or seroconvert. In summary, this study demonstrates that IDV causes a mild respiratory disease upon experimental infection of cattle and can be transmitted effectively among cattle by in-pen contact, but not from cattle to ferrets through fomite exposure. These findings support the hypothesis that cattle are a natural reservoir for the virus. IMPORTANCE A novel influenza virus, tentatively classified as influenza D virus (IDV), was identified in swine, cattle, sheep, and goats. Among these hosts, cattle have been proposed as the natural reservoir. In this study, we show that cattle experimentally infected with IDV can shed virus and transmit it to other cattle through direct contact, but not to ferrets through fomite routes. IDV caused minor clinical signs in the infected cattle, fulfilling another of Koch's postulates for this novel agent, although other objective clinical endpoints were not different from those of control animals. Although the disease observed was mild, IDV induced neutrophil tracking and epithelial attenuation in cattle trachea, which could facilitate coinfection with other pathogens, and in doing so, predispose animals to bovine respiratory disease.

A new member of the Orthomyxoviridae family, influenza D virus (IDV), was first reported in swine in the Midwest region of the United States. This study aims to extend our knowledge on the IDV epidemiology and to determine the impact of bovine production systems on virus spread. A total of 15 isolates were recovered from surveillance of bovine herds in Mississippi, and two genetic clades of viruses co-circulated in the same herd. Serologic assessment from neonatal beef cattle showed 94% seropositive, and presumed maternal antibody levels were substantially lower in animals over six months of age. Active IDV transmission was shown to occur at locations where young, weaned, and comingled calves were maintained. Serological characterization of archived sera suggested that IDV has been circulating in the Mississippi cattle populations since at least 2004. Continuous surveillance is needed to monitor the evolution and epidemiology of IDV in the bovine population.

Influenza D virus (IDV), a new member of the influenza virus family, was first reported in 2011 in swine in Oklahoma, USA, and then soon found in cattle across North America and Eurasia. Earlier studies suggested cattle serve as natural reservoir for IDV. The goal of this study is to perform a retrospective study looking at sera collected from Nebraska beef herds in 2003–2004 and 2014 for evidence of IDV antibodies. Results showed that all 40 randomly selected farms (2003–2004) we tested contained IDV seropositive adult animals and that approximately 98% of newborn calves (2014) had high levels of maternal antibodies against IDV. This study suggested that IDV exposures were present in Nebraska beef cattle since at least 2003.

Bovine respiratory disease (BRD) is a multifactorial disease complex and the leading infectious disease in post-weaned beef cattle. Clinical manifestations of BRD are recognized in beef calves within a high-risk setting, commonly associated with weaning, shipping, and novel feeding and housing environments. However, the understanding of complex host immune interactions and genomic mechanisms involved in BRD susceptibility remain elusive. Utilizing high-throughput RNA-sequencing, we contrasted the at-arrival blood transcriptomes of 6 beef cattle that ultimately developed BRD against 5 beef cattle that remained healthy within the same herd, differentiating BRD diagnosis from production metadata and treatment records. We identified 135 differentially expressed genes (DEGs) using the differential gene expression tools edgeR and DESeq2. Thirty-six of the DEGs shared between these two analysis platforms were prioritized for investigation of their relevance to infectious disease resistance using WebGestalt, STRING, and Reactome. Biological processes related to inflammatory response, immunological defense, lipoxin metabolism, and macrophage function were identified. Production of specialized pro-resolvin mediators (SPMs) and endogenous metabolism of angiotensinogen were increased in animals that resisted BRD. Protein-protein interaction modeling of gene products with significantly higher expression in cattle that naturally acquire BRD identified molecular processes involving microbial killing. Accordingly, identification of DEGs in whole blood at arrival revealed a clear distinction between calves that went on to develop BRD and those that resisted BRD. These results provide novel insight into host immune factors that are present at the time of arrival that confer protection from BRD.

Influenza D virus (IDV) has been identified in domestic cattle, swine, camelid, and small ruminant populations across North America, Europe, Asia, South America, and Africa. Our study investigated seroprevalence and transmissibility of IDV in feral swine. During 2012–2013, we evaluated feral swine populations in 4 US states; of 256 swine tested, 57 (19.1%) were IDV seropositive. Among 96 archived influenza A virus–seropositive feral swine samples collected from 16 US states during 2010–2013, 41 (42.7%) were IDV seropositive. Infection studies demonstrated that IDV-inoculated feral swine shed virus 3–5 days postinoculation and seroconverted at 21 days postinoculation; 50% of in-contact naive feral swine shed virus, seroconverted, or both. Immunohistochemical staining showed viral antigen within epithelial cells of the respiratory tract, including trachea, soft palate, and lungs. Our findings suggest that feral swine might serve an important role in the ecology of IDV.