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

  1. Jordan D. Zehr
  2. Sergei L. Kosakovsky Pond
  3. Darren P. Martin
  4. Kristina Ceres
  5. Gary R. Whittaker
  6. Jean K. Millet
  7. Laura B. Goodman
  8. Michael J. Stanhope

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Abstract

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 Alphacoronavirus 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.

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  1. Version published to 10.3390/v14050853
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    SciScore for 10.1101/2021.11.15.468709: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    In-frame nucleotide sequences were translated to amino-acids, aligned with MAFFT (Katoh and Standley 2013), and then mapped back to the nucleotide sequences to produce a codon-aware alignment.
    MAFFT
    suggested: (MAFFT, RRID:SCR_011811)
    We performed site-, branch-, and alignment-level selection tests based on the dN/dS (nonsynonymous / synonymous) ratio estimation as implemented in the HyPhy software package v.2.5.31 (Kosakovsky Pond et al. 2020).
    HyPhy
    suggested: (HyPhy, RRID:SCR_016162)
    2.3 Estimating divergence times: 2.3.1 Temporal signal: The temporal signal in each GARD partition was assessed using root-to-tip regression in TempEst v1.5.3 (Rambaut et al. 2016) and tip-dating-randomization tests (TDR) (Duchêne et al. 2015).
    TempEst
    suggested: (TempEst, RRID:SCR_017304)
    For each model tested, marginal likelihood was calculated using PathSampling (Lartillot & Philippe 2006) within the Model-Selection package in BEAST 2 with 12 steps, 1,000,000 MCMC steps with 25% burn-in, and an alpha of 0.3.
    BEAST
    suggested: (BEAST, RRID:SCR_010228)
    Bayesian phylogenies were created using 100 million MCMC steps in BEAST2, sampling every 10,000 steps.
    BEAST2
    suggested: (BEAST2, RRID:SCR_017307)
    Trees were summarized using the BEAST2 package TreeAnnotator v2.6.0, discarding 20% of trees as burn-in.
    TreeAnnotator
    suggested: (BEAST2, RRID:SCR_017307)
    Convergence of the MCMC chains was assessed using Tracer v1.7.1(Rambaut et al. 2018) and the effective sample size for each estimated parameter was confirmed to be greater than 200.
    Tracer
    suggested: (Tracer, RRID:SCR_019121)
    Phylogenetic trees were annotated using FigTree v1.4.4 (available from http://tree.bio.ed.ac.uk/software/figtree/).
    FigTree
    suggested: (FigTree, RRID:SCR_008515)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

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  3. Version published to 10.1101/2021.11.15.468709v1 on bioRxiv