Expression of canine distemper virus receptor nectin-4 in the central nervous system of dogs

Watanyoo Pratakpiriya,Angeline Ping Ping Teh,Ryoji Yamaguchi,Somporn Techangamsuwan,Araya Radtanakatikanon,Nopadon Pirarat,Makoto Takeda,Nguyen Thi Lan

doi:10.1038/s41598-017-00375-6

Abstract

Canine distemper virus (CDV) exhibits lymphotropic, epitheliotropic, and neurotropic nature, and causes a severe systemic infection in susceptible animals. Initially, signaling lymphocyte activation molecule (SLAM) expressed on immune cells has been identified as a crucial cellular receptor for CDV. Currently, nectin-4 expressed in epithelia has been shown to be another receptor for CDV. Our previous study demonstrated that neurons express nectin-4 and are infected with CDV. In this study, we investigated the distribution pattern of nectin-4 in various cell types in the canine central nervous system and showed its relation to CDV infection to further clarify the pathology of disease. Histopathological, immunohistochemical and immunofluorescent analyses were done using formalin-fixed paraffin-embedded tissues of CDV-infected dogs. Dual staining of nectin-4 and CDV antigen or nectin-4 and brain cell markers was performed. Nectin-4 was detected in ependymal cells, epithelia of choroid plexus, meningeal cells, neurons, granular cells, and Purkinje’s cells. CDV antigens were detected in these nectin-4-positive cells, further suggesting contribution of nectin-4 for the CDV neurovirulence. On the other hand, astrocytes did not express nectin-4, although they were frequently infected with CDV. Since astrocytes are negative for SLAM expression, they must express an unidentified CDV receptor, which also contributes to CDV neurovirulence.

Highlights

Canine distemper virus (CDV) is a highly virulent pathogen, which threatens various animals mainly in the order Carnivora
In a previous study we have isolated Asia-1 lineage CDV strains from 6 dogs (Nos 5, 6, 9–11, 13) and Asia-4 lineage CDV strains from 3 dogs (Nos 6, 8, 12) among the 13 CDV-infected dogs (Table 1)[11]
Many aspects in the CDV pathogenicity have been obtained, molecular mechanisms of CDV spread in the central nervous system (CNS) still remains unclear

Summary

Introduction

Canine distemper virus (CDV) is a highly virulent pathogen, which threatens various animals mainly in the order Carnivora. The H and F proteins play essential roles for virus entry They are critical for virus spread via cell-to-cell fusion. Our previous study demonstrated that a subset of neurons is infected with CDV and that they express nectin-4, suggesting the possible role of nectin-4 for the neurovirulence of CDV8. Contribution of nectin-4 for CDV spread in the CNS still remained to be studied, because, in addition to neurons, many types of neuronal and glial cells are infected with CDV in vivo[7, 9, 10]. This study aimed to reveal the distribution pattern of nectin-4 in canine tissues, especially in the CNS and to show correlation of CDV infection with the nectin-4 expression pattern of cells

Objectives

Methods

Results

Conclusion