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. 2021 Sep 15;10(9):1199.
doi: 10.3390/pathogens10091199.

Canine Morbillivirus from Colombian Lineage Exhibits In Silico and In Vitro Potential to Infect Human Cells

Santiago Rendon-Marin  1 , Carolina Quintero-Gil  1 , Diego Guerra  2 , Carlos Muskus  2 , Julian Ruiz-Saenz  1
Affiliations

Canine Morbillivirus from Colombian Lineage Exhibits In Silico and In Vitro Potential to Infect Human Cells

Santiago Rendon-Marin et al. Pathogens. .

Retraction in

Abstract

Canine morbillivirus (CDV) is a viral agent that infects domestic dogs and a vast array of wildlife species. It belongs to the Paramyxoviridae family, genus Morbillivirus, which is shared with the Measles virus (MeV). Both viruses employ orthologous cellular receptors, SLAM in mononuclear cells and Nectin-4 in epithelial cells, to enter the cells. Although CDV and MeV hemagglutinin (H) have similar functions in viral pathogenesis and cell tropism, the potential interaction of CDV-H protein with human cellular receptors is still uncertain. Considering that CDV is classified as a multi-host pathogen, the potential risk of CDV transmission to humans has not been fully discarded. In this study, we aimed to evaluate both in silico and in vitro, whether there is a cross-species transmission potential from CDV to humans. To accomplish this, the CDV-H protein belonging to the Colombian lineage was modelled. After model validations, molecular docking and molecular dynamics simulations were carried out between Colombian CDV-H protein and canine and human cellular receptors to determine different aspects of the protein-protein interactions. Moreover, cell lines expressing orthologous cellular receptors, with both reference and wild-type CDV strains, were conducted to determine the CDV cross-species transmission potential from an in vitro model. This in silico and in vitro approach suggests the possibility that CDV interacts with ortholog human SLAM (hSLAM) and human Nectin-4 receptors to infect human cell lines, which could imply a potential cross-species transmission of CDV from dogs to humans.

Keywords: Nectin-4; SLAM molecule; canine distemper; cellular receptor; inter-species transmission.

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Conflict of interest statement

The authors declare that they do not have anything to disclose regarding conflicts of interest with respect to this manuscript.

Figures

Figure 1
Figure 1
Hierarchical analysis of CVD-H amino acid sequences from diverse strains, including MeV-H protein sequence. The phylogenetic tree was inferred by the maximum likelihood method using a bootstrap of 1000. All the GenBank accession numbers and the viral protein are shown in all branches. Numbers on the nodes are the bootstrapping values for each clade. The CDV-H-South-3, Onderstepoort strain and MeV-H protein sequences are shown with a black filled circle, black filled diamond, and black filled square, respectively.
Figure 2
Figure 2
Homology models obtained by Modeller® and structural alignment with template. (A) The MeV-H protein used as template. PDB CODE: 2RKC. (B) Homology model of CDV-H-South-3 protein. (C) Structural alignment of 2RKC template (green) and CDV-H-South-3 protein model (light blue). (D) Structural alignment of hSLAM (green) and the cSLAM model (orange) as an example of modeled anine receptors.
Figure 3
Figure 3
Score values of the molecular docking by AutoDock Vina of peptides from different MeV or CDV strains.
Figure 4
Figure 4
Structural alignment from co-crystals of CDV-H or MeV-H protein with either human or canine SLAM and Nectin-4. Structural alignments between (A) the co-crystal of hSLAM (blue) and MeV-H protein (cyan) downloaded from the PDB (PDB Code: 3ALX) and the complex of cSLAM (orange) and CDV-H-South-3 (green) obtained by ClusPro and (B) the co-crystal of hNectin-4 (blue) and MeV-H protein (cyan) downloaded from the PDB (PDB Code: 4GJT) and the complex of cNectin-4 (orange) and CDV-H-South-3 (green) obtained by ClusPro.
Figure 5
Figure 5
CDV protein immunodetection using monoclonal antibodies in CELL-ELISA and immunoblotting. (A) Western blotting reference and wild-type CDV strains. Supernatants and Vero-Dog-SLAM cell lysates were submitted to 10% SDS-PAGE gels and analyzed with monoclonal antibodies to detect CDV proteins. Actin was measured as a constitutive gene, positive for cell lysates; Molecular Weight, MW; reference CDV supernatant, 1; Vero-Dog-SLAM cell lysates (negative control), 2; wild-type CDV supernatant, 3; reference CDV infected Vero-Dog-SLAM cell lysates, 4; wild-type CDV infected Vero-Dog-SLAM cell lysates, 5. (B) CELL-ELISA for CDV protein detection in reference and wild-type CDV strains.
Figure 6
Figure 6
Reference and wild-type CDV infection in both human and canine cell lines. U937, A549 and MCF-7 human cell lines and MDCK canine cell lines were infected with either reference or wild-type CDV. Vero-Dog-SLAM was employed as a positive control. Experiments on each cell line were performed by two independent experimental units with three replicas each (n = 6). Non-infected cells were employed as negative controls. Means and standard deviations are shown in the bar graph.
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References

    1. MacLachlan N., Dubovi E., Fenner F. Fenner’s Veterinary Virology. 4th ed. Elsevier; Amsterdam, The Netherlands: 2011. pp. 299–325.
    1. Martinez-Gutierrez M., Ruiz-Saenz J. Diversity of susceptible hosts in canine distemper virus infection: A systematic review and data synthesis. BMC Vet. Res. 2016;12:78. doi: 10.1186/s12917-016-0702-z. - DOI - PMC - PubMed
    1. da Fontoura Budaszewski R., Streck A.F., Nunes Weber M., Maboni Siqueira F., Muniz Guedes R.L., Wageck Canal C. Influence of vaccine strains on the evolution of canine distemper virus. Infect. Genet. Evol. 2016;41:262–269. doi: 10.1016/j.meegid.2016.04.014. - DOI - PubMed
    1. Lamb R.A., Parks G.D. Fields Virology. 6th ed. Wolters Kluwer Health Adis (ESP); Philadelphia, PA, USA: 2013. Paramyxoviridae.
    1. von Messling V., Zimmer G., Herrler G., Haas L., Cattaneo R. The hemagglutinin of canine distemper virus determines tropism and cytopathogenicity. J. Virol. 2001;75:6418–6427. doi: 10.1128/JVI.75.14.6418-6427.2001. - DOI - PMC - PubMed

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