Dog nectin-4 is an epithelial cell receptor for canine distemper virus that facilitates virus entry and syncytia formation
VIROLOGY
Authors: Noyce, Ryan S.; Delpeut, Sebastien; Richardson, Christopher D.
Abstract
Canine distemper virus (CDV) was shown to use dog nectin-4 as a receptor to gain entry into epithelial cells. RNA from dog placenta or MDCK kidney cells was isolated and cDNAs were prepared. Two splice variants of dog nectin-4 were identified. A deletion of 25 amino acids was found in the cytoplasmic domain of dog nectin-4 from MDCK cells, corresponding to a splice variant that is also seen in murine nectin-4, and did not affect its role as a receptor. Both dog nectin-4 and human nectin-4 could function as an entry factor for CDV containing an EGFP reporter gene. Inhibition of dog nectin-4 expression by RNAi or nectin-4 antibodies decreased CDV titers and EGFP fluorescence. Finally, dog nectin-4 also promotes syncytia formation, which could be inhibited by siRNA treatment. These data confirm that dog nectin-4 can be used by CDV to gain entry into epithelial cells, and facilitate virus spread. (C) 2012 Elsevier Inc. All rights reserved.
Using the ferret model to study morbillivirus entry, spread, transmission and cross-species infection
CURRENT OPINION IN VIROLOGY
Authors: Ludlow, Martin; Rennick, Linda J.; Nambulli, Sham; de Swart, Rik L.; Duprex, W. Paul
Abstract
Canine distemper virus (CDV) is an animal morbillivirus with a worldwide circulation that infects carnivores, including domestic dogs and an assortment of wildlife hosts. The development of reverse genetics systems for wild-type strains of CDV and the use of the resulting recombinant (r) viruses to infect ferrets by a natural route has shed new light on the temporal pathogenesis of distemper. Combining fluorescent protein expressing recombinant viruses and multimodal, macroscopic and microscopic imaging modalities has highlighted the differential role of the cellular receptors CD150 and PVRL4 in disease progression. This in turn has enabled pathways of viral spread, including multiple routes of entry into the central nervous system, to be mapped with unparalleled sensitivity.