OmniVira

Literature detail

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.

Jordan D Zehr1 Sergei L Kosakovsky Pond1 Darren P Martin2 Kristina Ceres3 Gary R Whittaker3,4 Jean K Millet5 Laura B Goodman3,6 Michael J Stanhope3
Affiliations 6 institutions
  1. Institute for Genomics and Evolutionary Medicine, Temple University, Philadelphia, PA 19122, USA.
  2. Computational Biology Division, Department of Integrative Biomedical Sciences, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Observatory, Cape Town 7549, South Africa.
  3. Department of Public and Ecosystem Health, Cornell University, Ithaca, NY 14853, USA.
  4. Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14853, USA.
  5. Unité de Virologie et Immunologie Moléculaires, UVSQ, INRAE, Université Paris-Saclay, 78350 Jouy-en-Josas, France.
  6. Baker Institute for Animal Health, Cornell University, Ithaca, NY 14850, USA.
PMID 35632597 2022 Viruses eng epublish
PubMed DOI Browse context

Article

Publication summary

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 <i>Alphacoronavirus</i> 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.

canine coronavirus coronavirus tropism shift feline coronavirus relaxed selection Coronavirus, Canine Animals Cats Dogs N-Acetylneuraminic Acid Spike Glycoprotein, Coronavirus Tropism Zoonoses

Structured evidence records

Evidence records

7 total
Spillover Event 2 records
Spillover Event Extraction confidence 0.95
Key finding

Canine coronavirus was identified in human samples from Malaysia and Haiti, indicating animal-to-human transmission.

Virus
CCoV
Location
Malaysia Malaysia
Supporting text

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.

Method
genetic analysis; evolutionary analysis
Study design
genomic surveillance
Transmission direction
animal-to-human
Geographic raw
Malaysia
Country inferred
Malaysia
Spillover Event Extraction confidence 0.95
Key finding

Canine coronavirus was identified in a human sample from Haiti, indicating animal-to-human transmission.

Virus
CCoV
Location
Haiti Haiti
Supporting text

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.

Method
genetic analysis; evolutionary analysis
Study design
genomic surveillance
Transmission direction
animal-to-human
Geographic raw
Haiti
Country inferred
Haiti
Cross Species Transmission 1 records
Cross Species Transmission Extraction confidence 0.88
Key finding

Genomic analysis revealed recombination between canine coronavirus and feline coronavirus, evidencing cross-species transmission between dog and cat hosts.

Virus
CCoV
Location
Not specified
Supporting text

The spike gene is extensively recombinant, with a feline coronavirus type II strain serving a prominent role in the recombinant history of the virus.

Method
evolutionary analyses; recombination analysis; phylogenetic analysis
Study design
phylogenetic analysis
Transmission direction
animal-to-animal
Genomic Evolution 1 records
Genomic Evolution Extraction confidence 0.90
Key finding

Evolutionary analyses of the canine coronavirus spike gene revealed recombination with feline coronavirus type II and evidence of relaxed selection and amino acid changes linked to tropism shift.

Virus
CCoV
Location
Not specified
Supporting text

We carried out detailed evolutionary analyses of the spike gene of this virus in the context of related Alphacoronavirus 1 species... 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.

Genes or proteins
spike gene; spike 0-domain
Analysis methods
evolutionary analysis; recombination analysis; molecular divergence time estimation
Molecular Adaptation 1 records
Molecular Adaptation Extraction confidence 0.93
Key finding

Mutations in the sialic acid binding region of the spike protein's 0-domain of a canine coronavirus are associated with relaxed selection and potential loss of enteric tropism, indicating molecular adaptation linked to cross-species infection.

Virus
CCoV
Host
Not specified
Location
Not specified
Supporting text

The spike 0-domain retains homology to CCoV2b and Transmissible Gastroenteritis Virus (TGEV), is subject to relaxed selection pressure, and contains unique amino acid substitutions within a region important for sialic acid binding and pathogenesis in TGEV, possibly causing loss of enteric tropism in the canine coronavirus detected in humans.

Genes or proteins
spike protein
Receptors
sialic acid receptor
Mechanism types
receptor_binding; tissue_tropism; pathogenicity
Receptor Usage 1 records
Receptor Usage Extraction confidence 0.75
Key finding

Mutations were identified in the sialic acid binding region of the spike 0-domain of canine coronavirus, indicating potential changes in receptor usage associated with altered tropism.

Virus
CCoV
Location
Not specified
Supporting text

It contains unique amino acid substitutions, including within a region important for sialic acid binding and pathogenesis in TGEV. 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.

Receptors
sialic acid
Recombination Or Reassortment 1 records
Recombination Or Reassortment Extraction confidence 0.90
Key finding

The canine coronavirus detected in human samples showed extensive recombination in the spike gene, with a feline coronavirus type II strain acting as a parental contributor.

Host
Not specified
Location
Not specified
Supporting text

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.

Event type
recombination
Genes or segments
spike