One world, one health, one virology of the mysterious labyrinth of coronaviruses: the canine coronavirus affair

Abstract

Human coronaviruses (HCoVs) often have animal origins and then adapt to humans by jumping directly or via an intermediate host. The emergence of SARS-CoV in 2003, MERS-CoV in 2012, and SARS-CoV-2 in late-2019, confirms that coronaviruses can cause severe-to-fatal disease and that bats are probably the source of these viruses, highlighting the role of animals as reservoirs.1Vlasova AN Diaz A Damtie D et al.Novel canine coronavirus isolated from a hospitalized pneumonia patient, east Malaysia.Clin Infect Dis. 2021; (published online May 20.)https://doi.org/10.1093/cid/ciab456Crossref PubMed Scopus (82) Google Scholar In 2017–18, a closely related, but distinct, canine coronavirus (CCoV) was identified for the first time in the nasopharyngeal swabs of children with pneumonia in Malaysia.1Vlasova AN Diaz A Damtie D et al.Novel canine coronavirus isolated from a hospitalized pneumonia patient, east Malaysia.Clin Infect Dis. 2021; (published online May 20.)https://doi.org/10.1093/cid/ciab456Crossref PubMed Scopus (82) Google Scholar The virus, CCoV-HuPn-2018, cultivated in the canine A72 cell line, was characterised as a novel canine-feline-like recombinant virus with a very unique deletion in the nucleoprotein. This feature was similar to the deletion found in SARS-CoV and SARS-CoV-2 that occurred very soon after introduction in humans, suggesting the zoonotic origin of CCoV-HuPn-2018. Analysis of the virus's genes highlights that CCoV-HuPn-2018 could have infected cats and pigs at one point, but it probably jumped directly from dogs into people, as the majority of the genome was the same as the CCoV strains, TN-449 and HLJ-073.1Vlasova AN Diaz A Damtie D et al.Novel canine coronavirus isolated from a hospitalized pneumonia patient, east Malaysia.Clin Infect Dis. 2021; (published online May 20.)https://doi.org/10.1093/cid/ciab456Crossref PubMed Scopus (82) Google Scholar This discovery focuses attention on CCoVs and to what these viruses have taught. Since the first report of CCoV in 1971, no great attention was given to this pathogen as it was commonly associated with mild gastroenteritis in dogs. But in the past few decades, the history of CCoV was characterised by the emergence of new viruses, some with pronounced pathogenic potential, which brought questions about their ability to undergo mutations and recombination.2Pratelli A The evolutionary processes of canine coronaviruses.Adv Virol. 2011; 2011562831Crossref PubMed Scopus (18) Google Scholar The fascinating evolutionary history of CCoVs is closely intermingled with the history of porcine transmissible gastroenteritis virus (TGEV) and the two feline coronavirus genotypes, feline coronavirus-1 (FCoV-1) and feline coronavirus-2 (FCoV-2). CCoV gave rise to FCoV-2 through homologous RNA recombination with FCoV-1 between the S and M genes.3Herrewegh AAPM Smeenk I Horzinek MC Rottier PJ de Groot RJ Feline coronavirus type II strains 79-1683 and 79-1146 originate from a double recombination between feline coronavirus type I and canine coronavirus.J Virol. 1998; 72: 4508-4514Crossref PubMed Google Scholar Furthermore, the analysis of the accessory protein gene, ORF3, highlighted that TGEV originated from CCoV through cross-species transmission.4Lorusso A Decaro N Schellen P et al.Gain, preservation, and loss of a group 1a coronavirus accessory glycoprotein.J Virol. 2008; 82: 10312-10317Crossref PubMed Scopus (69) Google Scholar Data have also suggested that two genotypes of CCoVs exist (CCoV-1 and CCoV-2). Phylogenetic analyses have shown that these viruses share up to 96% of nucleotide identity in the genome but have highly divergent S genes, and that CCoV-1 is more closely related to FCoV-1 than it is to CCoV-2;5Pratelli A Martella V Pistello M et al.Identification of coronaviruses in dogs that segregate separately from the canine coronavirus genotype.J Virol Methods. 2003; 107: 213-222Crossref PubMed Scopus (36) Google Scholar CCoV-2 has been well known since 1971 and is closely related to FCoV-2. In 2005, a highly virulent pantropic CCoV-2 strain, CB/05, was detected in dogs with a systemic fatal disease.6Buonavoglia C Decaro N Martella V et al.Canine coronavirus highly pathogenic for dogs.Emerg Infect Dis. 2006; 12: 492-494Crossref PubMed Scopus (141) Google Scholar Sequence analysis of the 3’ end of the CB/05 genome showed that it had a high amino acid identity to CCoV-2, although the S protein had the highest identity to FCoV-2, strain 79-1683. The virus induces severe clinical signs, lymphopenia, and infection of the lymphoid tissue, strongly suggesting that CCoVs can change their tropism, acquiring the ability to spread from the enteric tract to the internal organs.7Decaro N Mari V Elia G et al.Recombinant canine coronaviruses in dogs, Europe.Emerg Infect Dis. 2010; 16: 41-47Crossref PubMed Scopus (88) Google Scholar Additional data arose when CCoVs that had potential double recombinant origins, through partial S gene exchange with TGEV, were identified in dogs with gastroenteritis.8Decaro N Mari V Campolo M et al.Recombinant canine coronaviruses related to transmissible gastroenteritis virus of swine are circulating in dogs.J Virol. 2009; 83: 1532-1537Crossref PubMed Scopus (107) Google Scholar The analysis of a region of the genome (3’-end) of four recombinant viruses, and the analysis of the nearly full-lengh genome of two of those four strains, revealed the existence of the recombinant TGEV-like CCoVs. These events represent a kind of sliding door, in which the original CCoV gave rise to TGEV and, subsequently, TGEV gave rise to a TGEV-like CCoV onset. Considering the genetic and antigenic differences between the original and recombinant viruses, CCoV-2 was additionally divided into two different subtypes, CCoV-2a and CCoV-2b, which include reference and TGEV-like CCoV-2 isolates.8Decaro N Mari V Campolo M et al.Recombinant canine coronaviruses related to transmissible gastroenteritis virus of swine are circulating in dogs.J Virol. 2009; 83: 1532-1537Crossref PubMed Scopus (107) Google Scholar To assess the distribution of TGEV-like CCoVs, an epidemiological survey was done in European canine populations. About 20% of the CCoV-positive samples were characterised as TGEV-like CCoVs, confirming that the new virus effectively circulates in European countries.7Decaro N Mari V Elia G et al.Recombinant canine coronaviruses in dogs, Europe.Emerg Infect Dis. 2010; 16: 41-47Crossref PubMed Scopus (88) Google Scholar These findings underline the ability of CoVs to undergo recombination and genetic evolution, and to easily cross interspecies barriers. This high potential for genetic recombination ensures the proliferation of new strains that might have selective advantages over their parental genomes.9Dolja VV Carrington JC Evolution of positive-strand RNA viruses.Semin Virol. 1992; 3: 315-326Google Scholar The newly identified CCoV-Hupn-2018 should lead researchers to pay special attention to the mechanisms of recombination among coronaviruses, in addition to the onset of variants as a result of mutations. The recombination observed in CCoVs could be a warning sign for the evolution of SARS-CoV-2 and continuous monitoring of these viruses is required. We declare no competing interests.

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