Influenza C and D viral load in cattle correlates with bovine respiratory disease (BRD): Emerging role of orthomyxoviruses in the pathogenesis of BRD

Abstract

Bovine respiratory disease (BRD) is the costliest disease affecting the cattle industry globally. Orthomyxoviruses, influenza C virus (ICV) and influenza D virus (IDV) have recently been implicated to play a role in BRD. However, there are contradicting reports about the association of IDV and ICV to BRD. Using the largest cohort study (cattle, n = 599) to date we investigated the association of influenza viruses in cattle with BRD. Cattle were scored for respiratory symptoms and pooled nasal and pharyngeal swabs were tested for bovine viral diarrhea virus, bovine herpesvirus 1, bovine respiratory syncytial virus, bovine coronavirus, ICV and IDV by real-time PCR. Cattle that have higher viral loads of IDV and ICV also have greater numbers of co-infecting viruses than controls. More strikingly, 2 logs higher IDV viral RNA in BRD-symptomatic cattle that are co-infected animals than those infected with IDV alone. Our results strongly suggest that ICV and IDV may be significant contributors to BRD.

Successive Inoculations of Pigs with Porcine Reproductive and Respiratory Syndrome Virus 1 (PRRSV-1) and Swine H1N2 Influenza Virus Suggest a Mutual Interference between the Two Viral Infections

“…Although further investigations are needed to more deeply decipher the complex interplays between PRRSV and swIAV infections, these findings provide new insight into PRDC regulation in pigs [2]. They should be relevant as well for the comprehensive understanding of respiratory virus co-infections in other species, such as within bovine respiratory disease in cattle [57], or in humans where co-infections may occur with influenza A virus and other viruses [58], among which some exhibit an ability to interfere with the IFN pathway.…”

Influenza D virus in respiratory disease in Canadian, province of Québec, cattle: Relative importance and evidence of new reassortment between different clades

“…was higher in co-infections than in mono-infections, suggesting that the level of clinical severity of infection might be related to some specific association of pathogens. Despite of recent field study evidenced that IDV viral load in cattle correlates with BRDC (Nissly et al, 2020), more studies are needed to confirm this hypothesis. In addition, the strategy of IDV to interact with airway epithelium should be more studied since other viruses of the BRDC follow different strategies for this interaction (BPiV-3 preferentially targets the apical membrane with ciliated cells, BoHV-1 mainly targets basal cells, while BRSV neither targets differentiated epithelial cells nor basal cells but well sub-epithelial cells) (Goris et al, 2009;Kirchhoff et al, 2014).…”

“…Recently, no relationship was found between BRDC development in Western Canada and the number of viruses detected by metagenomics, or the presence of any specific individual virus or combination of viruses (Zhang et al, 2020). However, another study evidenced that IDV viral load in cattle correlates with BRDC (Nissly et al, 2020).…”

Sialic Acid Receptors: The Key to Solving the Enigma of Zoonotic Virus Spillover

“…Influenza C and D viruses (ICVs and IDVs) use membrane protein hemagglutinin-esterase fusion (HEF) to detect and bind to N-acetyl-9, O acetylneuraminic acid receptors [ 48 ]. The zoonotic potential of ICVs and IDVs is yet to be investigated [ 90 , 91 , 92 , 93 , 94 , 95 ]. Other orthomyxoviruses, such as the infectious salmon anemia (ISA) virus affecting fish, have a preferential binding toward 4-O-Acetylated SAs [ 96 , 97 ].…”