Recent Zoonotic Spillover and Tropism Shift of a Canine Coronavirus Is Associated with Relaxed Selection and Putative Loss of Function in NTD Subdomain of Spike Protein

• Published in: Viruses 2022-04, Vol.14 (5), p.853
• Main Authors: Zehr, Jordan D, Pond, Sergei L Kosakovsky, Martin, Darren P, Ceres, Kristina, Whittaker, Gary R, Millet, Jean K, Goodman, Laura B, Stanhope, Michael J
• Format: Article
• Language: English
• Subjects: Adaptation; Amino acids; Animal biology; Animals; Biochemistry, Molecular Biology; Brief Report; canine coronavirus; Cats; coronavirus tropism shift; Coronavirus, Canine; Coronaviruses; Disease transmission; Divergence; Dogs; Emerging diseases; feline coronavirus; Gastroenteritis; Genomes; Genomics; Heparan sulfate; Homology; Human health and pathology; Life Sciences; Molecular evolution; N-Acetylneuraminic Acid; Proteins; relaxed selection; Spike Glycoprotein, Coronavirus - genetics; Spike protein; Transmissible gastroenteritis; Tropism; Vertebrate Zoology; Viruses; Zoonoses
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v14050853

A canine coronavirus (CCoV) has now been reported from two independent human samples from Malaysia (respiratory, collected in 2017-2018; CCoV-HuPn-2018) and Haiti (urine, collected in 2017); these two viruses were nearly genetically identical. In an effort to identify any novel adaptations associated with this apparent shift in tropism we carried out detailed evolutionary analyses of the spike gene of this virus in the context of related 1 species. The spike 0-domain retains homology to CCoV2b (enteric infections) and Transmissible Gastroenteritis Virus (TGEV; enteric and respiratory). This domain is subject to relaxed selection pressure and an increased rate of molecular evolution. It contains unique amino acid substitutions, including within a region important for sialic acid binding and pathogenesis in TGEV. Overall, the spike gene is extensively recombinant, with a feline coronavirus type II strain serving a prominent role in the recombinant history of the virus. Molecular divergence time for a segment of the gene where temporal signal could be determined, was estimated at around 60 years ago. We hypothesize that the virus had an enteric origin, but that it may be losing that particular tropism, possibly because of mutations in the sialic acid binding region of the spike 0-domain.