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. Despite decades of research, the pathophysiology of BRD is not yet fully understood. It is widely believed that viruses predispose cattle to bacterial infection by causing direct damage to the respiratory tract and interfering with the immune system, leading to bacterial pneumonia. BRD remains a major challenge despite extensive vaccination against all major viral pathogens associated with the disease. Orthomyxoviruses (Influenza C & D viruses), have recently been found to infect cattle throughout the United States and are implicated to play a role in BRD. Here, we use the largest cohort study to date to investigate the association of influenza viruses in cattle with BRD. Cattle (n=599) from 3 locations were individually observed and scored for respiratory symptoms using the McGuirk scoring system. Deep pharyngeal and mid-nasal swabs were collected from each animal and were tested quantitatively for bovine viral diarrhea virus, bovine herpesvirus 1, bovine respiratory syncytial virus, bovine coronavirus, influenza C virus (ICV) and influenza D virus (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, in BRD-symptomatic cattle, the geometric mean of detectable IDV viral RNA was nearly 2 logs higher in co-infected animals (1.30x104) than those singly infected with IDV (2.19x102). This is strong evidence that viral coinfections can lead to higher replication of IDV. Our results strongly suggest that orthomyxoviruses may be significant contributors to BRD.