Understanding the mechanisms of viral and bacterial coinfections in bovine respiratory disease: a comprehensive literature review of experimental evidence

Abstract

Bovine respiratory disease (BRD) is one of the most important diseases impacting the global cattle industry, resulting in significant economic loss. Commonly referred to as shipping fever, BRD is especially concerning for young calves during transport when they are most susceptible to developing disease. Despite years of extensive study, managing BRD remains challenging as its aetiology involves complex interactions between pathogens, environmental and host factors. While at the beginning of the twentieth century, scientists believed that BRD was only caused by bacterial infections ("bovine pasteurellosis"), we now know that viruses play a key role in BRD induction. Mixtures of pathogenic bacteria and viruses are frequently isolated from respiratory secretions of animals with respiratory illness. The increased diagnostic screening data has changed our understanding of pathogens contributing to BRD development. In this review, we aim to comprehensively examine experimental evidence from all existing studies performed to understand coinfections between respiratory pathogens in cattle. Despite the fact that pneumonia has not always been successfully reproduced by in vivo calf modelling, several studies attempted to investigate the clinical significance of interactions between different pathogens. The most studied model of pneumonia induction has been reproduced by a primary viral infection followed by a secondary bacterial superinfection, with strong evidence suggesting this could potentially be one of the most common scenarios during BRD onset. Different in vitro studies indicated that viral priming may increase bacterial adherence and colonization of the respiratory tract, suggesting a possible mechanism underpinning bronchopneumonia onset in cattle. In addition, a few in vivo studies on viral coinfections and bacterial coinfections demonstrated that a primary viral infection could also increase the pathogenicity of a secondary viral infection and, similarly, dual infections with two bacterial pathogens could increase the severity of BRD lesions. Therefore, different scenarios of pathogen dynamics could be hypothesized for BRD onset which are not limited to a primary viral infection followed by a secondary bacterial superinfection.

Keywords: Bovine respiratory disease; bacterial superinfection; cattle; coinfections; experimental infections; in vitro; influenza D virus; respiratory bacteria; respiratory viruses.

Figure 1

Timeline showing examples on the history of BRD pathogens discovery and adopted countermeasures throughout the years. An emphasis on vaccine countermeasures taken in Europe was given.

Figure 2

Heat map showing the impact of sequential coinfections on respiratory pathology in cattle on in vivo experiments. On the y-axis, the virus used for the primary viral infection is represented. On the x-axis, the pathogen used for the secondary superinfection is listed. The severity of coinfections on in vivo studies (compared to single pathogens) was given a score from 1 to 4 (colour code for the score is given in function of the increase in clinical signs, light orange to dark orange). The description of the scoring system that we used to describe the impact of coinfection in vivo is available as Additional file 1. Cell values represent the mean between the scores given to different in vivo studies performed with the same pathogens. The value in parentheses represents the number of trials carried out for each couple of pathogens that were used to calculate the mean score. White cells indicate an absence of in vivo studies for that specific couple of pathogens. *: the two pathogens were simultaneously inoculated in some studies.