Tropism and pathological findings associated with canine respiratory coronavirus (CRCoV)

Judy A Mitchell,Harriet W Brooks,Balázs Szladovits,Kerstin Erles,Rachel Gibbons,Shelly Shields,Joe Brownlie

doi:10.1016/j.vetmic.2012.11.025

Abstract

Canine infectious respiratory disease (CIRD) occurs frequently in densely housed dog populations. One of the common pathogens involved is canine respiratory coronavirus (CRCoV), however little is known regarding its pathogenesis and the role it plays in the development of CIRD. The pathogenesis of five geographically unrelated canine respiratory coronavirus (CRCoV) isolates was investigated. Following experimental infection in dogs, all five CRCoV isolates gave rise to clinical signs of respiratory disease consistent with that observed during natural infection. The presence of CRCoV was associated with marked histopathological changes in the nares and trachea, with loss and damage to tracheal cilia, accompanied by inflammation. Viral shedding was readily detected from the oropharynx up to 10 days post infection, but there was little or no evidence of rectal shedding. The successful re-isolation of CRCoV from a wide range of respiratory and mucosal associated lymphoid tissues, and lung lavage fluids demonstrates a clear tropism of CRCoV for respiratory tissues and fulfils the final requirement for Koch's postulates. By study day 14 dogs had seroconverted to CRCoV and the antibodies raised were neutralising against both homologous and heterologous strains of CRCoV in vitro, thus demonstrating antigenic homogeneity among CRCoV strains from the two continents. Defining the role that CRCoV and other agents play in CIRD is a considerable, but important, challenge if the disease is to be managed, treated and prevented more successfully. Here we have successfully developed a model for studying the pathogenicity and the role of CRCoV in CIRD.

Highlights

In that study we demonstrated that young dogs were susceptible to experimental infection with both canine respiratory coronavirus (CRCoV) isolates, which gave rise to clinical signs of respiratory disease consistent with naturally occurring infection
It is worth noting that in both instances these dogs were euthanized on study day 14 and displayed the clinical signs of respiratory disease recorded throughout the 14-day study period, the scores were highest in these two dogs on study days 10–13
Previous publications have collectively demonstrated the global distribution of CRCoV and its association with respiratory disease in dogs under field conditions (Erles et al, 2003; Decaro et al, 2007; Kaneshima et al, 2006; Priestnall et al, 2006, 2007; Yachi and Mochizuki, 2006; Knesl et al, 2009)

Summary

Introduction

Canine infectious respiratory disease (CIRD) is a disease complex which occurs frequently in densely housed dog populations such as in rehoming, training and boarding kennels, and is usually characterised by a dry hacking cough, though it may progress to a potentially fatalManagement of CIRD is problematic due to the multifactorial nature of the disease in which a number of organisms including Bordetella bronchiseptica (Bemis, 1992; Bemis et al, 1977; Keil and Fenwick, 1998), canine parainfluenza virus (Appel and Percy, 1970; Erles et al, 2004); canine adenovirus-2 (Ditchfield et al, 1962); canine herpesvirus (Erles and Brownlie, 2005; Karpas et al, 1968) and Mycoplasma spp. (Bemis, 1992; Chalker et al, 2004) are known to be involved. Through the use of an in vitro tracheal explant culture system, a moderate reduction in ciliary function and a down-regulation of pro-inflammatory cytokine mRNA levels (TNF-a, IL-6 and the chemokine IL-8) was observed in response to CRCoV exposure (Priestnall et al, 2009). Such alterations in the mucociliary and innate immune systems could be linked to increased susceptibility to secondary infection and is consistent with the proposed role for CRCoV in CIRD. Given the global presence of this virus, insight into CRCoV pathogenesis among isolates originating from geographically distinct locations would be valuable to determine the need for a global vaccine

Methods

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Conclusion