Rendon-Marin Santiago, Quintero-Gil Carolina, Guerra Diego, Muskus Carlos, Ruiz-Saenz Julian
Grupo de Investigación en Ciencias Animales-GRICA, Facultad de Medicina Veterinaria y Zootecnia, Universidad Cooperativa de Colombia, sede Bucaramanga, 680002 Bucaramanga, Colombia.
Programa para el Estudio y Control de Enfermedades Tropicales-PECET, Facultad de Medicina, Universidad de Antioquia, 050010 Medellín, Colombia.
Pathogens. 2021 Sep 15;10(9):1199. doi: 10.3390/pathogens10091199.
(CDV) is a viral agent that infects domestic dogs and a vast array of wildlife species. It belongs to the 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.
犬瘟热病毒（CDV）是一种病毒病原体，可感染家犬和众多野生动物物种。它属于副黏病毒科麻疹病毒属，与麻疹病毒（MeV）同属该属。两种病毒都利用直系同源细胞受体，即单核细胞中的信号淋巴细胞激活分子（SLAM）和上皮细胞中的连接黏附分子4（Nectin-4）进入细胞。尽管CDV和MeV血凝素（H）在病毒发病机制和细胞嗜性方面具有相似功能，但CDV-H蛋白与人类细胞受体的潜在相互作用仍不确定。鉴于CDV被归类为多宿主病原体，CDV传播给人类的潜在风险尚未被完全排除。在本研究中，我们旨在通过计算机模拟和体外实验评估CDV是否存在跨物种传播给人类的可能性。为实现这一目标，对属于哥伦比亚谱系的CDV-H蛋白进行了建模。在模型验证后，对哥伦比亚CDV-H蛋白与犬类和人类细胞受体进行了分子对接和分子动力学模拟，以确定蛋白质-蛋白质相互作用的不同方面。此外，使用表达直系同源细胞受体的细胞系，分别与参考株和野生型CDV毒株进行实验，以从体外模型确定CDV的跨物种传播潜力。这种计算机模拟和体外实验方法表明，CDV有可能与直系同源人类SLAM（hSLAM）和人类Nectin-4受体相互作用以感染人类细胞系，这可能意味着CDV存在从犬类向人类的潜在跨物种传播。
