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Canine enteric coronavirus

Professor Alan Radford and Dr Jenny Stavisky examine the clinical signs, epidemiology, diagnosis and treatment of a ribonucleic acid (RNA) virus, where most infections result in mild clinical signs of enteritis, or subclinical infection.

Canine enteric coronavirus (CECoV) belongs to the coronavirus family. While this large family of viruses includes some important human pathogens, it is important to emphasise that CECoV is not closely related to human coronaviruses like severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), the cause of COVID-19. The two viruses are completely distinct.

Coronaviruses can evolve rapidly because they have a high error rate during replication. They can also swap pieces of genome by recombination. Having the largest genome of positive-stranded RNA virus (approximately 30,000 base pairs) permits a high degree of genomic adaptability, allowing these viruses to tolerate changes in their genome whilst maintaining function. Coronaviruses are surrounded by a lipid envelope, a thin fatty layer derived from the cell they infect. This makes coronaviruses relatively fragile. Generally they survive poorly in the environment and are readily inactivated by soap-based cleansers and disinfectants.

Types of coronavirus

The coronavirus family is divided into three distinct groups or genera - alpha, beta and gammas.

Alphacoronaviruses

Canine enteric coronavirus belongs to the alphacoronaviruses, along with feline coronavirus (FeCoV, the causative agent of feline infectious peritonitis (FIP)) and transmissible gastroenteritis of pigs (TGEV). These three viruses are very closed related. Indeed, it has been shown that CeCoV can induce seroconversion in pigs and clinical signs similar to those of FeCoV in cats.

There are types of both FeCoV and CECoV and it appears that they share a history of recombination between each other. For example, type 2 FeCoV was formed from a double recombination event between type 1 FeCoV and type 2 CECoV. Despite this close relationship, one important distinction remains. FeCoV has not so far been found to infect dogs. However, both experimental and natural infections of cats with CECoV have occasionally been reported, resulting in clinical signs similar to FIP. Investigation of these two viruses may reveal further evidence of cross-species transmission.

Betacoronaviruses

Betacoronaviruses contain a diverse range of viruses, including the recently-emerged severe acute respiratory syndrome (SARS)-CoV2 (the causeof COVID-19), as well as the original SARS-CoV that emerged in 2002, and Middle East respiratory syndrome coronavirus from 2012 (MERS-CoV). These viruses are relatively closely related to each other and a range of viruses in wildlife species like bats which they may have evolved.

Canine respiratory coronavirus (CRCoV) is a completely distinct member of this group and believed to form part of the Canine Infectious Respiratory Disease (CIRD, or "kennel cough") complex. Other important members of the betacoronavirus group include mouse hepatitus virus (MHV) which is used in many experimental models of coronavirus biology, as well as human coronavirus (HCoV) OC43, bovine coronavirus (BCoV) and equine coronavirus (ECV), which are associated with respiratory (HCoV) or enteric (BCoV, ECV) infections in their target species.

Gammacoronaviruses

Gammacoronaviruses mainly consist of avian respiratory viruses, the most notable of which is infectious bronchitis virus (IBV), a disease seen mainly in poultry production.

Clinical signs

Most CECoV infections result in mild clinical signs of enteritis, or in some cases, subclinical infection. Infection is normally faeco-oral, and the virus primarily replicates in the small intestinal villi, resulting in desquamation and malabsorptive diarrhoea. However, there are also sporadic reports of more severe disease, typically in young puppies, likely associated with viral mutations.

Virulent strains are characterised by an ability to infiltrate multiple organs, including the lungs, kidneys and brain. In some cases, gene deletions have been implicated in the increased virulence. Clinical signs include severe, haemorrhagic diarrhoea, vomiting, anorexia and lethargy, and the disease can be fatal in some cases.

Epidemiology

CECoV was first identified in 1971 from an outbreak of diarrhoea in military dogs (Binn 1974). Since then, it has been recognised across the world in canids. Evidence of infection has also been found in other families including mustelids and Ursidae (bears). The initial studies recognised what is now known as type II CECoV, probably because virus isolation in cell culture was the best test at the time, and type I CECoV has so far never been cultured in vitro. Indeed, the presence of type I CECoV was not identified until 2003, when molecular methods such as polymerase chain reaction (PCR) test and sequencing became widely available. 

The risk of CECoV infection differs between household pet dogs and dogs kept in groups. In household pet dogs, while exposure to CECoV appears to be relatively common, with seroprevalence ranging from 15.8% to 54%, carriage of the virus appears fairly uncommon. Kennelled dogs appear to be at a heightened risk with dogs undergoing both clinical and subclinical infection. It seems likely that there are factors associated with kennels, such as hygiene and stocking density, as well as factors including pre-existing immunity and health status, which affect both the spread of CECoV in a kennel and a dog’s response to infection.

Diagnosis

Molecular diagnostic tests based on reverse transcription PCR are now commercially available, sometimes as part of diarrhoea panels. 

Treatment 

There is no specific treatment for CECoV and indeed, many mild cases will resolve spontaneously. Severe cases may resemble canine parvovirus infection clinically and both require similarly aggressive symptomatic treatment, including intravenous fluid therapy, intensive nursing care and, where secondary bacterial infection occurs, appropriate antibacterial therapy. Although not licensed for CECoV, some suggest the antiviral properties of interferon may provide some benefit in severe cases.

Prevention

Although available some years ago, there are currently no CECoV vaccines licensed in the UK. Their use has been associated with some controversy, possibly due to severe adverse reactions seen in a proportion of dogs following use of an early vaccine preparation.

In the absence of vaccination, prevention largely relies on the use of management practices to decrease the risk of spread of the virus. CECoV is environmentally labile, and therefore practising good hygiene and the use of appropriate disinfectants should help limit transmission in an outbreak.

References

  • Binn, L.N., Lazar, E.C., Keenan, K.P., Huxsoll, D.L., Marchwicki, R.H., Strano, A.J., 1974, Recovery and characterisation of a coronavirus from military dogs with diarrohea. Proceedings, annual meeting of the United States Animal Health Association, 359
  • Buonavoglia, C., Decaro, N., Martella, V., Elia, G., Campolo, M., Desario, C., Castagnaro, M., Tempesta, M., 2006, Canine coronavirus highly pathogenic for dogs. Emerging Infectious Diseases 12, 492-494
  • Chen S, Liu D, Tian J, Kang H, Guo D, Jiang Q, Liu J, Li Z, Hu X, Qu L (2019). Molecular characterisation of HLJ-073, a recombinant canine coronavirus strain from China with an ORF3abc deletion. Archives of Virology. 164(8):2159-2164
  • Decaro, N., Campolo, M., Lorusso, A., Desario, C., Mari, V., Colaianni, M.L., Elia, G., Martella, V., Buonavoglia, C., 2008a, Experimental infection of dogs with a novel strain of canine coronavirus causing systemic disease and lymphopenia. Veterinary Microbiology 128, 253-260
  • Decaro N, Cordonnier N, Demeter Z, Egberink H, Elia G, Grellet A, Le Poder S, Mari V, Martella V, Ntafis V, von Reitzenstein M, Rottier PJ, Rusvai M, Shields S, Xylouri E, Xu Z, Buonavoglia C (2013). European surveillance for pantropic canine coronavirus. Journal of Clinical Microbiology 51(1):83-8
  • Stavisky J, Pinchbeck G, Gaskell RM, Dawson S, German AJ, Radford AD (2012). Cross sectional and longitudinal surveys of canine enteric coronavirus infection in kennelled dogs: a molecular marker for biosecurity. Infection, Genetics and Evolution 12(7):1419-26
  • Tennant, B.J., Gaskell, R.M., Jones, R.C., Gaskell, C.J., 1993, Studies on the epizootiology of canine coronavirus. Veterinary Record 132, 7-11
  • Zappulli, V., Caliari, D., Cavicchioli, L., Tinelli, A., Castagnaro, M., 2007, Systemic fatal type II coronavirus infection in a dog: pathological findings and immunohistochemistry. Research in Veterinary Science.

Authors

Find out more about one of the authors of this article, Professor Alan Radford.