Canine distemper virus with the intact C protein has the potential to replicate in human epithelial cells by using human nectin4 as a receptor

Abstract

Recent outbreaks in monkeys have proven that canine distemper virus (CDV) causes diseases in a wide range of mammals. CDV uses SLAM and nectin4 as receptors to replicate in susceptible animals. Here, we show that human nectin4, but not human SLAM, is fully functional as a CDV receptor. The CDV Ac96I strain hardly replicated in nectin4-expressing human epithelial NCI-H358 cells, but readily adapted to grow in them. Unsurprisingly, no amino acid change in the H protein was required for the adaptation. The original Ac96I strain possessed a truncated C protein, and a subpopulation possessing the intact C protein was selected after growth in NCI-H358 cells. Other CDV strains possessing the intact C protein showed significantly higher growth abilities in NCI-H358 cells than the Ac96I strain with the truncated C protein. These findings suggest that the C protein is functional in human epithelial cells and critical for CDV replication in them.

Canine Distemper Virus Associated with a Lethal Outbreak in Monkeys Can Readily Adapt To Use Human Receptors

“…In addition, our recent study suggested that CDV has the potential to counteract the human interferon system and replicate in human cells (12). Accordingly, CDV should be seriously considered a potential threat for humans.…”

“…In part, this receptor specificity generates a species barrier for morbilliviruses. On the other hand, nectin-4, another morbillivirus receptor (8)(9)(10), is highly conserved in its amino acid sequence among different mammals and, thus, may play only a minor role in determining the host specificity of morbilliviruses (11,12). Recently, however, CDV outbreaks have emerged in a variety of mammals, including nonhuman primates, and showed high mortality rates (11,(13)(14)(15).…”

“…This CDV strain was designated CYN07-hV. The replication kinetics of CYN07-hV were analyzed in Vero cells expressing canine receptors (Vero.DogSLAMtag and Vero/dNectin4) (10), macaque receptors (Vero/macSLAM and Vero/macNectin4) (11), and human receptors (Vero/hSLAM and Vero/hNectin4) (12) and in the parental Vero cells. Although CYN07-hV replicated inefficiently in the parental Vero cells, its replication rates were greatly enhanced in all other cell lines expressing the canine, macaque, and human receptors, including Vero/hSLAM cells (Fig.…”

Recent Host Range Expansion of Canine Distemper Virus and Variation in Its Receptor, the Signaling Lymphocyte Activation Molecule, in Carnivores

“…Amino acid sequences for SLAM are variable among host species, and some key residues are important for virus binding (Ohno et al 2003). In contrast, nectin-4 is highly conserved among mammals, and no specificity has been reported among morbilliviruses (Otsuki et al 2013). Thus, SLAM is more likely than nectin-4 to play a crucial role in determination of host-virus specificity.…”

Intracellular Transport of the Measles Virus Ribonucleoprotein Complex Is Mediated by Rab11A-Positive Recycling Endosomes and Drives Virus Release from the Apical Membrane of Polarized Epithelial Cells

“…We found that MDCK cells were to some extent susceptible to the IC323 strain infection, as observed from the infection with the laboratoryadapted Edmonston strain (6). Using Vero cells expressing canine and human nectin4 (33,34), we found that canine nectin4 functions as an MV receptor as well as human nectin4 (data not shown). It was recently reported that MDCK cells express canine nectin4 (35).…”