Abstract

Canine distemper virus (CDV), a paramyxovirus, causes a severe highly contagious lethal disease in carnivores, such as mink. Mink lung epithelial cells (Mv.1.Lu cells) are sensitive to CDV infection and are homologous to the natural host system of mink. The current study analyzed the response of Mv.1.Lu cells to CDV infection by iTRAQ combined with LC–MS/MS. In total, 151 and 369 differentially expressed proteins (DEPs) were markedly up-regulated or down-regulated, respectively. Thirteen DEPs were validated via real-time RT-PCR or western blot analysis. Network and KEGG pathway analyses revealed several regulated proteins associated with the NF-κB signaling pathway. Further validation was performed by western blot analysis and immunofluorescence assay, which demonstrated that different CDV strains induced NF-κB P65 phosphorylation and nuclear translocation. Moreover, the results provided interesting information that some identified DEPs possibly associated with the pathogenesis and the immune response upon CDV infection. This study is the first overview of the responses to CDV infection in Mv.1.Lu cells, and the findings will help to analyze further aspects of the molecular mechanisms involved in viral pathogenesis and the immune responses upon CDV infection.

Highlights

  • Canine distemper virus (CDV), a negative-sense, single-stranded RNA virus, belonging to the genus Morbillivirus, family Paramyxoviridae, causes a severe highly contagious lethal disease in carnivores, such as dogs, lions, ferrets, raccoon dogs, foxes, and minks (Williams et al, 1988; Deem et al, 2000; Martella et al, 2010; Zhao et al, 2010; Viana et al, 2015)

  • A previous study demonstrated the capacity of CDV growth in Mv.1.Lu cells (Lednicky et al, 2004), we initially confirmed the ability of PS replication in Mv.1.Lu cells and established the growth kinetics of PS replication

  • The molecular mechanisms involved in viral pathogenesis and host immune responses have not been fully elucidated

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Summary

Introduction

Canine distemper virus (CDV), a negative-sense, single-stranded RNA virus, belonging to the genus Morbillivirus, family Paramyxoviridae, causes a severe highly contagious lethal disease in carnivores, such as dogs, lions, ferrets, raccoon dogs, foxes, and minks (Williams et al, 1988; Deem et al, 2000; Martella et al, 2010; Zhao et al, 2010; Viana et al, 2015). Many studies have reported the effects of CDV infections on the host cell proteins, such as inhibiting STAT1 and STAT2 nuclear import (Rothlisberger et al, 2010), inducing cytokine responses in PBMCs (Nielsen et al, 2009), and inducing lymphocytes apoptosis (Kumagai et al, 2004). Most of these reports have primarily investigated a single host cell protein or partially selected proteins and the mechanisms of CDV pathogenesis and immunomodulation have not been fully elucidated. More details associated with host responses to CDV infection should shed some light on potential targets for antiviral agents

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